Editing Candida albicans

{{Short description|Species of fungus}}
{{cs1 config|name-list-style=vanc}}{{Speciesbox
| image = SEM of C albicans.tif
| image_caption = ''Candida albicans'' visualized using scanning electron microscopy. Note the abundant hyphal mass.
| genus = Candida
| species = albicans
| authority = ([[Charles-Philippe Robin|C.-P. Robin]]) [[Christine Marie Berkhout|Berkhout]] (1923)
| synonyms = *''Candida stellatoidea''<ref>[https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=5476&lvl=3&lin=f&keep=1&srchmode=1&unlock Candida albicans at NCBI Taxonomy browser] {{Webarchive|url=https://web.archive.org/web/20181215225924/https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=5476&lvl=3&lin=f&keep=1&srchmode=1&unlock |date=2018-12-15 }}, url accessed 2006-12-26</ref>
* ''Monilia albicans''<ref name="The yeasts"/>
* ''Oidium albicans''<ref>{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | display-authors = 6 | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 137–164 | date = May 1952 | pmid = 32166015 | doi = 10.2307/2394509 | jstor = 2394509 | pmc = 7052475 }}</ref>
* and many others.<ref>{{cite web |url=http://www.speciesfungorum.org/Names/SynSpecies.asp?RecordID=256187 |title=Synonymy of Candida albicans |website=speciesfungorum.org |access-date=8 December 2021 |archive-date=8 December 2021 |archive-url=https://web.archive.org/web/20211208173643/http://www.speciesfungorum.org/Names/SynSpecies.asp?RecordID=256187 |url-status=live }}</ref>
}}

'''''Candida albicans''''' is an opportunistic [[pathogenic yeast]]<ref name="Gow2017">{{cite journal | vauthors = Gow NA, Yadav B | title = Microbe Profile: Candida albicans: a shape-changing, opportunistic pathogenic fungus of humans | journal = Microbiology | volume = 163 | issue = 8 | pages = 1145–1147 | date = August 2017 | pmid = 28809155 | doi = 10.1099/mic.0.000499 | doi-access = free | hdl = 2164/12360 | hdl-access = free }}</ref> that is a common member of the human [[gut flora]]. It can also survive outside the human body.<ref>{{cite journal | vauthors = Bensasson D, Dicks J, Ludwig JM, Bond CJ, Elliston A, Roberts IN, James SA | title = Diverse Lineages of ''Candida albicans'' Live on Old Oaks | journal = Genetics | volume = 211 | issue = 1 | pages = 277–288 | date = January 2019 | pmid = 30463870 | pmc = 6325710 | doi = 10.1534/genetics.118.301482 }}</ref><ref>{{cite book| vauthors = Odds FC |title=Candida and Candidosis: A Review and Bibliography|date=1988|publisher=Bailliere Tindall|location=London; Philadelphia|isbn=978-0702012655|edition=2nd|url-access=registration|url=https://archive.org/details/manualofcardiacd0000khan}}</ref> It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults.<ref name="Kerawala 2010">{{cite book |veditors=Kerawala C, Newlands C |title=Oral and maxillofacial surgery |year=2010 |publisher=Oxford University Press |location=Oxford |isbn=978-0-19-920483-0 |pages=446, 447}}</ref><ref name="SIFO">{{cite journal | vauthors = Erdogan A, Rao SS | title = Small intestinal fungal overgrowth | journal = Current Gastroenterology Reports | volume = 17 | issue = 4 | pages = 16 | date = April 2015 | pmid = 25786900 | doi = 10.1007/s11894-015-0436-2 | s2cid = 3098136 }}</ref> It is usually a [[commensal]] organism, but it can become [[pathogen]]ic in [[immunodeficiency|immunocompromised]] individuals under a variety of conditions.<ref name="SIFO"/><ref name="pmid24789109"/> It is one of the few species of the genus ''[[Candida (fungus)|Candida]]'' that cause the human infection [[candidiasis]], which results from an overgrowth of the fungus.<ref name="SIFO"/><ref name="pmid24789109"/> Candidiasis is, for example, often observed in [[HIV]]-infected patients.<ref name="Calderone"/>
''C. albicans'' is the most common fungal species isolated from [[biofilm]]s either formed on (permanent) implanted medical devices or on human [[Tissue (biology)|tissue]].<ref name=Kumamoto2002>{{cite journal | vauthors = Kumamoto CA | title = Candida biofilms | journal = Current Opinion in Microbiology | volume = 5 | issue = 6 | pages = 608–611 | date = December 2002 | pmid = 12457706 | doi = 10.1016/s1369-5274(02)00371-5 }}</ref><ref name=Donlan2001>{{cite journal | vauthors = Donlan RM | title = Biofilm formation: a clinically relevant microbiological process | journal = Clinical Infectious Diseases | volume = 33 | issue = 8 | pages = 1387–1392 | date = October 2001 | pmid = 11565080 | doi = 10.1086/322972 | doi-access = free }}</ref> ''C. albicans'', [[Candida tropicalis|''C. tropicalis'']], [[Candida parapsilosis|''C. parapsilosis'']], and [[Candida glabrata|''C. glabrata'']] are together responsible for 50–90% of all cases of candidiasis in humans.<ref name="pmid24789109"/><ref name="Pfaller">{{cite journal | vauthors = Pfaller MA, Diekema DJ | title = Epidemiology of invasive candidiasis: a persistent public health problem | journal = Clinical Microbiology Reviews | volume = 20 | issue = 1 | pages = 133–163 | date = January 2007 | pmid = 17223626 | pmc = 1797637 | doi = 10.1128/CMR.00029-06 }}</ref><ref>{{cite journal | vauthors = Schlecht LM, Peters BM, Krom BP, Freiberg JA, Hänsch GM, Filler SG, Jabra-Rizk MA, Shirtliff ME | display-authors = 6 | title = Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue | journal = Microbiology | volume = 161 | issue = Pt 1 | pages = 168–181 | date = January 2015 | pmid = 25332378 | pmc = 4274785 | doi = 10.1099/mic.0.083485-0 | doi-access = free }}</ref> A mortality rate of 40% has been reported for patients with systemic candidiasis due to ''C. albicans''.<ref>{{cite book| vauthors = Singh R, Chakrabarti A | veditors = Prasad R |title=Candida albicans: Cellular and Molecular Biology|date=2017|publisher=Springer International Publishing AG|location=Switzerland|isbn=978-3-319-50408-7|page=27|edition=2|chapter=Invasive Candidiasis in the Southeast-Asian Region}}</ref> By one estimate, invasive candidiasis contracted in a hospital causes 2,800 to 11,200 deaths yearly in the US.<ref name="Pfaller"/> Nevertheless, these numbers may not truly reflect the true extent of damage this organism causes, given  studies indicating that ''C. albicans'' can cross the [[blood–brain barrier]] in mice.<ref>{{cite journal | vauthors = Wu Y, Du S, Johnson JL, Tung HY, Landers CT, Liu Y, Seman BG, Wheeler RT, Costa-Mattioli M, Kheradmand F, Zheng H, Corry DB | display-authors = 6 | title = Microglia and amyloid precursor protein coordinate control of transient Candida cerebritis with memory deficits | journal = Nature Communications | volume = 10 | issue = 1 | pages = 58 | date = January 2019 | pmid = 30610193 | pmc = 6320369 | doi = 10.1038/s41467-018-07991-4 | bibcode = 2019NatCo..10...58W }}</ref><ref>{{cite web | url=https://medicalxpress.com/news/2019-01-fungi-brain-infection-impair-memory.html | title=Fungi cause brain infection and impair memory in mice | access-date=2019-01-04 | archive-date=2023-11-20 | archive-url=https://web.archive.org/web/20231120131239/https://medicalxpress.com/news/2019-01-fungi-brain-infection-impair-memory.html | url-status=live }}</ref>

''C. albicans'' is commonly used as a [[model organism]] for fungal pathogens.<ref name="Kabir">{{cite journal | vauthors = Kabir MA, Hussain MA, Ahmad Z | title = Candida albicans: A Model Organism for Studying Fungal Pathogens | journal = ISRN Microbiology | volume = 2012 | pages = 538694 | date = 2012 | pmid = 23762753 | pmc = 3671685 | doi = 10.5402/2012/538694 | doi-access = free }}</ref> It is generally referred to as a [[dimorphic fungus]] since it grows both as [[yeast]] and [[hypha|filamentous]] cells. However, it has several different [[#Morphology|morphological]] phenotypes including opaque, GUT, and pseudohyphal forms.<ref>{{cite journal | vauthors = Kadosh D | title = Regulatory mechanisms controlling morphology and pathogenesis in Candida albicans | journal = Current Opinion in Microbiology | volume = 52 | pages = 27–34 | date = December 2019 | pmid = 31129557 | pmc = 6874724 | doi = 10.1016/j.mib.2019.04.005 }}</ref><ref>{{cite book | vauthors = Basso V, d'Enfert C, Znaidi S, Bachellier-Bassi S | title = Fungal Physiology and Immunopathogenesis | chapter = From Genes to Networks: The Regulatory Circuitry Controlling Candida albicans Morphogenesis | series = Current Topics in Microbiology and Immunology | volume = 422 | pages = 61–99 | date = 2019 | pmid = 30368597 | doi = 10.1007/82_2018_144 | isbn = 978-3-030-30236-8 }}</ref> ''C. albicans'' was for a long time considered an obligate diploid organism without a haploid stage. This is, however, not the case. Next to a haploid stage ''C. albicans'' can also exist in a tetraploid stage. The latter is formed when diploid ''C. albicans'' cells mate when they are in the opaque form.<ref name=" Hickman">{{cite journal | vauthors = Hickman MA, Zeng G, Forche A, Hirakawa MP, Abbey D, Harrison BD, Wang YM, Su CH, Bennett RJ, Wang Y, Berman J | display-authors = 6 | title = The 'obligate diploid' Candida albicans forms mating-competent haploids | journal = Nature | volume = 494 | issue = 7435 | pages = 55–59 | date = February 2013 | pmid = 23364695 | pmc = 3583542 | doi = 10.1038/nature11865 | bibcode = 2013Natur.494...55H }}</ref> The diploid genome size is approximately 29&nbsp;Mb, and up to 70% of the protein coding genes have not yet been characterized.<ref name="candidagenome.org">{{cite web|url=http://www.candidagenome.org/cache/C_albicans_SC5314_genomeSnapshot.html|title=Candida albicans SC5314 Genome Snapshot/Overview|website=www.candidagenome.org|access-date=27 March 2018|archive-date=16 November 2018|archive-url=https://web.archive.org/web/20181116021638/http://www.candidagenome.org/cache/C_albicans_SC5314_genomeSnapshot.html|url-status=live}}</ref>
''C. albicans'' is easily cultured in the lab and can be studied both ''in vivo'' and ''in vitro''. Depending on the media different studies can be done as the media influences the morphological state of ''C. albicans''. A special type of medium is CHROMagar ''Candida'', which can be used to identify different ''Candida'' species.<ref>{{cite journal | vauthors = Sevilla MJ, Odds FC | title = Development of Candida albicans hyphae in different growth media--variations in growth rates, cell dimensions and timing of morphogenetic events | journal = Journal of General Microbiology | volume = 132 | issue = 11 | pages = 3083–3088 | date = November 1986 | pmid = 3305781 | doi = 10.1099/00221287-132-11-3083 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Odds FC, Bernaerts R | title = CHROMagar Candida, a new differential isolation medium for presumptive identification of clinically important Candida species | journal = Journal of Clinical Microbiology | volume = 32 | issue = 8 | pages = 1923–1929 | date = August 1994 | pmid = 7989544 | pmc = 263904 | doi = 10.1128/JCM.32.8.1923-1929.1994 }}</ref>

==Etymology==
"''Candida albicans''" can be read as [[tautology (language)|tautological]]. "[[wikt:Candida#Etymology|Candida]]" comes from the Latin word "[[wikt:candidus#Adjective|candidus]]", meaning "shining white". "[[wikt:albicans#Etymology|Albicans]] itself is the present participle of the Latin word "[[wikt:albico#Verb|albicō]]", meaning "becoming white". This leads to one possible interpretation as the redundant phrase "pure white becoming white".{{citation needed|date=August 2022}}<!-- Insert citation:

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It is often shortly referred to as thrush, candidiasis, or candida.
More than a hundred synonyms have been used to describe ''C. albicans''.<ref name="The yeasts">{{cite book|title=The yeasts, a taxonomic study|date=1998|isbn=978-0444813121|edition=4| vauthors = Kurtzman CP, Fell JW |publisher=Elsevier }}</ref><ref>{{cite web | vauthors = Simi V | title = Origin of the Names of Species of Candida | url = http://www.antimicrobe.org/h04c.files/history/candida-history.pdf | access-date = 2017-05-17 | archive-date = 2015-06-21 | archive-url = https://web.archive.org/web/20150621055659/http://www.antimicrobe.org/h04c.files/history/candida-history.pdf | url-status = live }}</ref>
Over 200 species have been described within the candida genus. The oldest reference to thrush, most likely caused by ''C. albicans'', dates back to 400 BC in [[Hippocrates]]' work ''Of the Epidemics'' describing oral candidiasis.<ref name="The yeasts"/><ref>{{cite web | vauthors = McCool L | title = The Discovery and Naming of Candida albicans | url = http://www.antimicrobe.org/h04c.files/history/DiscoveryNaming%20of%20CandidaAlbicans.pdf | access-date = 2017-05-17 | archive-date = 2018-05-05 | archive-url = https://web.archive.org/web/20180505083908/http://antimicrobe.org/h04c.files/history/DiscoveryNaming%20of%20CandidaAlbicans.pdf | url-status = live }}</ref>

==Genome==
[[File:Candida Gram stain.jpg|thumb|right|''Candida albicans'' visualized by Gram stain and microscopy. Note the hyphae and chlamydospores, which are 2–4 μm in diameter.]]

[[File:Candida albicans PHIL 3192 lores.jpg|thumb|''Candida albicans'' growing on [[Sabouraud agar]]]]

The genome of ''C. albicans'' is almost 16Mb for the haploid size (28Mb for the diploid stage) and consists of 8 sets of chromosome pairs called chr1A, chr2A, chr3A, chr4A, chr5A, chr6A, chr7A and {{not a typo|chrRA}}. The second set (''C. albicans'' is diploid) has similar names but with a B at the end. Chr1B, chr2B, ... and chrRB. The whole genome contains 6,198 [[open reading frame]]s (ORFs). Seventy percent of these ORFs have not yet been characterized. The whole genome has been sequenced making it one of the first fungi to be completely sequenced (next to ''Saccharomyces cerevisiae'' and ''Schizosaccharomyces pombe'').<ref name="Calderone"/><ref name="candidagenome.org"/> All open reading frames (ORFs) are also available in [[Gateway Technology|Gateway-adapted vectors]]. Next to this ORFeome there is also the availability of a GRACE (gene replacement and conditional expression) library to study essential genes in the genome of ''C. albicans''.<ref name="Large-scale essential gene identifi">{{cite journal | vauthors = Roemer T, Jiang B, Davison J, Ketela T, Veillette K, Breton A, Tandia F, Linteau A, Sillaots S, Marta C, Martel N, Veronneau S, Lemieux S, Kauffman S, Becker J, Storms R, Boone C, Bussey H | display-authors = 6 | title = Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery | journal = Molecular Microbiology | volume = 50 | issue = 1 | pages = 167–181 | date = October 2003 | pmid = 14507372 | doi = 10.1046/j.1365-2958.2003.03697.x | s2cid = 6773779 | doi-access =  }}</ref><ref name="ReferenceB">{{cite web|url=http://www.candidagenome.org/CommunityNews.shtml|title=Candida Community News|website=www.candidagenome.org|access-date=27 March 2018|archive-date=27 October 2018|archive-url=https://web.archive.org/web/20181027230229/http://www.candidagenome.org/CommunityNews.shtml|url-status=live}}</ref> The most commonly used strains to study ''C. albicans'' are the WO-1 and SC5314 strains. The WO-1 strain is known to switch between white-opaque form with higher frequency while the SC5314 strain is the strain used for gene sequence reference.<ref>{{cite web|url=http://www.candidagenome.org/Strains.shtml#P37005|title=Candida Strains|website=www.candidagenome.org|access-date=27 March 2018|archive-date=27 October 2018|archive-url=https://web.archive.org/web/20181027232139/http://www.candidagenome.org/Strains.shtml#P37005|url-status=live}}</ref>

One of the most important features of the ''C. albicans'' genome is the high heterozygosity. At the base of this heterozygosity lies the occurrence of numeric and structural [[chromosome|chromosomal]] rearrangements and changes as means of generating genetic diversity by chromosome length polymorphisms (contraction/expansion of repeats), reciprocal [[chromosomal translocation|translocations]], chromosome [[Deletion (genetics)|deletions]], Nonsynonymous [[single-nucleotide polymorphism]]s and [[trisomy]] of individual chromosomes. These [[karyotype|karyotypic]] alterations lead to changes in the phenotype, which is an [[adaptation]] strategy of this fungus. These mechanisms are further being explored with the availability of the complete analysis of the ''C. albicans'' genome.<ref>{{cite journal | vauthors = Rustchenko-Bulgac EP | title = Variations of Candida albicans electrophoretic karyotypes | journal = Journal of Bacteriology | volume = 173 | issue = 20 | pages = 6586–6596 | date = October 1991 | pmid = 1917880 | pmc = 208996 | doi = 10.1128/jb.173.20.6586-6596.1991 }}</ref><ref>{{cite journal | vauthors = Holmes AR, Tsao S, Ong SW, Lamping E, Niimi K, Monk BC, Niimi M, Kaneko A, Holland BR, Schmid J, Cannon RD | display-authors = 6 | title = Heterozygosity and functional allelic variation in the Candida albicans efflux pump genes CDR1 and CDR2 | journal = Molecular Microbiology | volume = 62 | issue = 1 | pages = 170–186 | date = October 2006 | pmid = 16942600 | doi = 10.1111/j.1365-2958.2006.05357.x | doi-access =  | s2cid = 11838673 }}</ref><ref>{{cite journal | vauthors = Jones T, Federspiel NA, Chibana H, Dungan J, Kalman S, Magee BB, Newport G, Thorstenson YR, Agabian N, Magee PT, Davis RW, Scherer S | display-authors = 6 | title = The diploid genome sequence of Candida albicans | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 19 | pages = 7329–7334 | date = May 2004 | pmid = 15123810 | pmc = 409918 | doi = 10.1073/pnas.0401648101 | doi-access = free | bibcode = 2004PNAS..101.7329J }}</ref>

An unusual feature of the genus ''Candida'' is that in many of its species (including ''C. albicans'' and ''C. tropicalis'', but not, for instance, ''C. glabrata'') the CUG [[Genetic code|codon]], which normally specifies leucine, specifies serine in these species. This is an unusual example of a departure from the standard [[genetic code]], and most such departures are in [[start codon]]s or, for [[eukaryote]]s, [[genetic code#Variations|mitochondrial genetic codes]].<ref>{{cite journal | vauthors = Ohama T, Suzuki T, Mori M, Osawa S, Ueda T, Watanabe K, Nakase T | title = Non-universal decoding of the leucine codon CUG in several Candida species | journal = Nucleic Acids Research | volume = 21 | issue = 17 | pages = 4039–4045 | date = August 1993 | pmid = 8371978 | pmc = 309997 | doi = 10.1093/nar/21.17.4039 }}</ref><ref>{{cite web |url=http://www.candidagenome.org/help/code_tables.shtml |title=CGD Help: Non-standard Genetic Codes |author1=Arnaud, MB |author2=Costanzo, MC |author3=Inglis, DO |author4=Skrzypek, MS |author5=Binkley, J |author6=Shah, P |author7=Binkley, G |author8=Miyasato, SR |author9=Sherlock, G |work=Candida Genome Database |access-date=30 October 2011 |archive-date=1 November 2018 |archive-url=https://web.archive.org/web/20181101015358/http://www.candidagenome.org/help/code_tables.shtml |url-status=live }}</ref><ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi#SG12 |title=The Alternative Yeast Nuclear Code |author=Andrzej (Anjay) Elzanowski and Jim Ostell |publisher=National Center for Biotechnology Information (NCBI) |location=Bethesda, Maryland, U.S.A. |date=7 July 2010 |access-date=30 October 2011 |work=The Genetic Codes |archive-date=13 May 2011 |archive-url=https://web.archive.org/web/20110513014234/http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi#SG12 |url-status=live }}</ref> This alteration may, in some environments, help these ''Candida'' species by inducing a permanent stress response, a more generalized form of the [[heat shock response]].<ref>{{cite journal | vauthors = Santos MA, Cheesman C, Costa V, Moradas-Ferreira P, Tuite MF | title = Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp | journal = Molecular Microbiology | volume = 31 | issue = 3 | pages = 937–947 | date = February 1999 | pmid = 10048036 | doi = 10.1046/j.1365-2958.1999.01233.x | s2cid = 28572737 | doi-access = free }}</ref> However, this different codon usage makes it more difficult to study ''C. albicans'' protein-protein interactions in the model organism ''S. cerevisiae''. To overcome this problem a ''C. albicans'' specific two-hybrid system was developed.<ref name="stynen">{{cite journal | vauthors = Stynen B, Van Dijck P, Tournu H | title = A CUG codon adapted two-hybrid system for the pathogenic fungus Candida albicans | journal = Nucleic Acids Research | volume = 38 | issue = 19 | pages = e184 | date = October 2010 | pmid = 20719741 | pmc = 2965261 | doi = 10.1093/nar/gkq725 }}</ref>

The genome of ''C. albicans'' is highly dynamic, contributed by the different CUG translation, and this variability has been used advantageously for molecular epidemiological studies and population studies in this species. The genome sequence has allowed for identifying the presence of a [[parasexual cycle]] (no detected [[meiosis|meiotic division]]) in ''C. albicans''.<ref name=Butler>{{cite journal | vauthors = Butler G, Rasmussen MD, Lin MF, Santos MA, Sakthikumar S, Munro CA, Rheinbay E, Grabherr M, Forche A, Reedy JL, Agrafioti I, Arnaud MB, Bates S, Brown AJ, Brunke S, Costanzo MC, Fitzpatrick DA, de Groot PW, Harris D, Hoyer LL, Hube B, Klis FM, Kodira C, Lennard N, Logue ME, Martin R, Neiman AM, Nikolaou E, Quail MA, Quinn J, Santos MC, Schmitzberger FF, Sherlock G, Shah P, Silverstein KA, Skrzypek MS, Soll D, Staggs R, Stansfield I, Stumpf MP, Sudbery PE, Srikantha T, Zeng Q, Berman J, Berriman M, Heitman J, Gow NA, Lorenz MC, Birren BW, Kellis M, Cuomo CA | display-authors = 6 | title = Evolution of pathogenicity and sexual reproduction in eight Candida genomes | journal = Nature | volume = 459 | issue = 7247 | pages = 657–662 | date = June 2009 | pmid = 19465905 | pmc = 2834264 | doi = 10.1038/nature08064 | bibcode = 2009Natur.459..657B }}</ref> This study of the evolution of sexual reproduction in six ''Candida'' species found recent losses in components of the major meiotic crossover-formation pathway, but retention of a minor pathway.<ref name=Butler/> The authors suggested that if ''Candida'' species undergo meiosis it is with reduced machinery, or different machinery, and indicated that unrecognized meiotic cycles may exist in many species. In another evolutionary study, introduction of partial CUG identity redefinition (from ''Candida'' species) into ''Saccharomyces cerevisiae'' clones caused a stress response that negatively affected sexual reproduction. This CUG identity redefinition, occurring in ancestors of ''Candida'' species, was thought to lock these species into a diploid or polyploid state with possible blockage of sexual reproduction.<ref>{{cite journal | vauthors = Silva RM, Paredes JA, Moura GR, Manadas B, Lima-Costa T, Rocha R, Miranda I, Gomes AC, Koerkamp MJ, Perrot M, Holstege FC, Boucherie H, Santos MA | display-authors = 6 | title = Critical roles for a genetic code alteration in the evolution of the genus Candida | journal = The EMBO Journal | volume = 26 | issue = 21 | pages = 4555–4565 | date = October 2007 | pmid = 17932489 | pmc = 2063480 | doi = 10.1038/sj.emboj.7601876 }}</ref>

==Morphology==
''C. albicans'' exhibits a wide range of [[morphology (biology)|morphologica]]l [[phenotype]]s due to phenotypic switching and bud to hypha transition. The yeast-to-hyphae transition (filamentation) is a rapid process and induced by environmental factors. Phenotypic switching is spontaneous, happens at lower rates and in certain strains up to seven different phenotypes are known. The best studied switching mechanism is the white to opaque switching (an epigenetic process). Other systems have been described as well. Two systems (the high-frequency switching system and white to opaque switching) were discover by [[David R. Soll]] and colleagues.<ref name="auto">{{cite journal | vauthors = Slutsky B, Staebell M, Anderson J, Risen L, Pfaller M, Soll DR | title = "White-opaque transition": a second high-frequency switching system in Candida albicans | journal = Journal of Bacteriology | volume = 169 | issue = 1 | pages = 189–197 | date = January 1987 | pmid = 3539914 | pmc = 211752 | doi = 10.1128/jb.169.1.189-197.1987 }}</ref><ref name="High-frequency switching of colony">{{cite journal | vauthors = Slutsky B, Buffo J, Soll DR | title = High-frequency switching of colony morphology in Candida albicans | journal = Science | volume = 230 | issue = 4726 | pages = 666–669 | date = November 1985 | pmid = 3901258 | doi = 10.1126/science.3901258 | bibcode = 1985Sci...230..666S }}</ref> Switching in ''C. albicans'' is often, but not always, influenced by environmental conditions such as the level of CO<sub>2</sub>, anaerobic conditions, medium used and temperature.<ref name="High-frequency switching in Candida">{{cite journal | vauthors = Soll DR | title = High-frequency switching in Candida albicans | journal = Clinical Microbiology Reviews | volume = 5 | issue = 2 | pages = 183–203 | date = April 1992 | pmid = 1576587 | pmc = 358234 | doi = 10.1128/cmr.5.2.183 }}</ref>
In its yeast form ''C. albicans'' ranges from 10 to 12 [[Micrometre|microns]].<ref>{{cite book |vauthors=Reiss E, DiSalvo A |veditors=Hunt RC |title=Microbiology and Immunology On-line |date=2018 |url=https://www.microbiologybook.org/mycology/2018mycology-3.htm |access-date=7 September 2020 |chapter=Mycology - Yeasts |archive-date=3 January 2021 |archive-url=https://web.archive.org/web/20210103011954/http://www.microbiologybook.org/mycology/2018mycology-3.htm |url-status=live }}</ref> Spores can form on the pseudohyphae called [[chlamydospore]]s which survive when put in unfavorable conditions such as dry or hot seasons.<ref name="microbewiki.kenyon.edu">{{cite web | url = https://microbewiki.kenyon.edu/index.php/Candida_albicans | vauthors = Foss S | date = 22 July 2013 | title = Candida albicans | access-date = 24 October 2017 | archive-date = 18 November 2023 | archive-url = https://web.archive.org/web/20231118161321/https://microbewiki.kenyon.edu/index.php/Candida_albicans | url-status = live }}</ref>
[[File:Candida albicans mixed colony.jpg|thumb|An opaque colony of ''C. albicans'' growing as yeast-like cells with filamentous ''C. albicans'' cells on top]]

===Yeast-to-hypha switching===

Although often referred to as '''dimorphic''', ''C. albicans'' is, in fact, [[polyphenism|polyphenic]] (often also referred to as [[pleomorphism (microbiology)|pleomorphic]]).<ref>{{cite journal | vauthors = Staniszewska M, Bondaryk M, Siennicka K, Kurzatkowski W | title = Ultrastructure of Candida albicans pleomorphic forms: phase-contrast microscopy, scanning and transmission electron microscopy | journal = Polish Journal of Microbiology | volume = 61 | issue = 2 | pages = 129–135 | year = 2012 | pmid = 23163212 | doi = 10.33073/pjm-2012-016 | doi-access = free }}</ref> When cultured in standard yeast laboratory medium, ''C. albicans'' grows as ovoid "yeast" cells. However, mild environmental changes in temperature, CO<sub>2</sub>, nutrients and pH can result in a morphological shift to filamentous growth.<ref>{{cite journal | vauthors = Si H, Hernday AD, Hirakawa MP, Johnson AD, Bennett RJ | title = Candida albicans white and opaque cells undergo distinct programs of filamentous growth | journal = PLOS Pathogens | volume = 9 | issue = 3 | pages = e1003210 | date = March 2013 | pmid = 23505370 | pmc = 3591317 | doi = 10.1371/journal.ppat.1003210 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sudbery PE | title = Growth of Candida albicans hyphae | journal = Nature Reviews. Microbiology | volume = 9 | issue = 10 | pages = 737–748 | date = August 2011 | pmid = 21844880 | doi = 10.1038/nrmicro2636 | s2cid = 205498076 }} See [https://www.nature.com/articles/nrmicro2636#figure-title figure 2] {{Webarchive|url=https://web.archive.org/web/20181215142754/https://www.nature.com/articles/nrmicro2636#figure-title |date=2018-12-15 }}.</ref> Filamentous cells share many similarities with yeast cells. Both cell types seem to play a specific, distinctive role in the survival and pathogenicity of ''C. albicans''. Yeast cells seem to be better suited for the dissemination in the bloodstream while hyphal cells have been proposed as a virulence factor. Hyphal cells are invasive and speculated to be important for tissue penetration, colonization of organs and surviving plus escaping macrophages.<ref>{{cite journal | vauthors = Sudbery P, Gow N, Berman J | title = The distinct morphogenic states of Candida albicans | journal = Trends in Microbiology | volume = 12 | issue = 7 | pages = 317–324 | date = July 2004 | pmid = 15223059 | doi = 10.1016/j.tim.2004.05.008 }}</ref><ref>{{cite journal | vauthors = Jiménez-López C, Lorenz MC | title = Fungal immune evasion in a model host-pathogen interaction: Candida albicans versus macrophages | journal = PLOS Pathogens | volume = 9 | issue = 11 | pages = e1003741 | year = 2013 | pmid = 24278014 | pmc = 3836912 | doi = 10.1371/journal.ppat.1003741 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Berman J, Sudbery PE | title = Candida Albicans: a molecular revolution built on lessons from budding yeast | journal = Nature Reviews. Genetics | volume = 3 | issue = 12 | pages = 918–930 | date = December 2002 | pmid = 12459722 | doi = 10.1038/nrg948 | s2cid = 29341377 }}</ref> The transition from yeast to hyphal cells is termed to be one of the key factors in the virulence of ''C. albicans''; however, it is not deemed necessary.<ref>{{cite journal | vauthors = Shareck J, Belhumeur P | title = Modulation of morphogenesis in Candida albicans by various small molecules | journal = Eukaryotic Cell | volume = 10 | issue = 8 | pages = 1004–1012 | date = August 2011 | pmid = 21642508 | pmc = 3165445 | doi = 10.1128/EC.05030-11 }}</ref> When ''C. albicans'' cells are grown in a medium that mimics the physiological environment of a human host, they grow as filamentous cells (both true hyphae and pseudohyphae). ''C. albicans'' can also form [[chlamydospore]]s, the function of which remains unknown, but it is speculated they play a role in surviving harsh environments as they are most often formed under unfavorable conditions.<ref name="Staib2007">{{cite journal | vauthors = Staib P, Morschhäuser J | title = Chlamydospore formation in Candida albicans and Candida dubliniensis--an enigmatic developmental programme | journal = Mycoses | volume = 50 | issue = 1 | pages = 1–12 | date = January 2007 | pmid = 17302741 | doi = 10.1111/j.1439-0507.2006.01308.x | s2cid = 7387908 }}</ref>

The cAMP-PKA signaling cascade is crucial for the morphogenesis and an important transcriptional regulator for the switch from yeast like cells to filamentous cells is EFG1.<ref>{{cite journal | vauthors = Sohn K, Urban C, Brunner H, Rupp S | title = EFG1 is a major regulator of cell wall dynamics in Candida albicans as revealed by DNA microarrays | journal = Molecular Microbiology | volume = 47 | issue = 1 | pages = 89–102 | date = January 2003 | pmid = 12492856 | doi = 10.1046/j.1365-2958.2003.03300.x | s2cid = 23743789 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Shapiro RS, Robbins N, Cowen LE | title = Regulatory circuitry governing fungal development, drug resistance, and disease | journal = Microbiology and Molecular Biology Reviews | volume = 75 | issue = 2 | pages = 213–267 | date = June 2011 | pmid = 21646428 | pmc = 3122626 | doi = 10.1128/MMBR.00045-10 }}</ref>
[[File:Whiteopaquecandida.jpg|Round, white-phase and elongated, opaque-phase ''Candida albicans'' cells: the scale bar is 5 μm|thumb]]
[[File:Whiteopaqueregulation.jpg|thumb|In this model of the genetic network regulating the white-opaque switch, the white and gold boxes represent genes enriched in the white and opaque states, respectively. The blue lines represent relationships based on genetic epistasis. Red lines represent Wor1 control of each gene, based on Wor1 enrichment in chromatin immunoprecipitation experiments. Activation (arrowhead) and repression (bar) are inferred based on white- and opaque-state expression of each gene.]]

===High-frequency switching===

Besides the well-studied yeast-to-hyphae transition other switching systems have been described.<ref>{{cite journal | vauthors = Soll DR | title = The role of phenotypic switching in the basic biology and pathogenesis of Candida albicans | journal = Journal of Oral Microbiology | volume = 6 | issue = 2 | pages = 895–9 | date = January 2014 | pmid = 24455104 | pmc = 3895265 | doi = 10.3402/jom.v6.22993 }}</ref> One such system is the "high-frequency switching" system. During this switching different cellular morphologies ([[phenotype]]s) are generated spontaneously. This type of switching does not occur en masse, represents a variability system and it happens independently from environmental conditions.<ref name="High-frequency switching in Candida"/> The strain 3153A produces at least seven different colony morphologies.<ref>{{cite journal | vauthors = Alby K, J R | title = To switch or not to switch?: Phenotypic switching is sensitive to multiple inputs in a pathogenic fungus | journal = Communicative & Integrative Biology | volume = 2 | issue = 6 | pages = 509–511 | date = November 2009 | pmid = 20195457 | pmc = 2829826 | doi = 10.4161/cib.2.6.9487 }}</ref><ref name="High-frequency switching of colony"/><ref>{{cite journal | vauthors = Vargas K, Wertz PW, Drake D, Morrow B, Soll DR | title = Differences in adhesion of Candida albicans 3153A cells exhibiting switch phenotypes to buccal epithelium and stratum corneum | journal = Infection and Immunity | volume = 62 | issue = 4 | pages = 1328–1335 | date = April 1994 | pmid = 8132340 | pmc = 186281 | doi = 10.1128/IAI.62.4.1328-1335.1994 }}</ref> In many strains the different phases convert spontaneously to the other(s) at a low frequency. The switching is reversible, and colony type can be inherited from one generation to another.
Being able to switch through so many different (morphological) phenotypes makes ''C. albicans'' able to grow in different environments, both as a commensal and as a pathogen.<ref name="ReferenceC"/>

In the 3153A strain, a gene called [[Sirtuin 2|''SIR2'']] (for silent information regulator), which seems to be important for phenotypic switching, has been found.<ref>{{cite journal | vauthors = Pérez-Martín J, Uría JA, Johnson AD | title = Phenotypic switching in Candida albicans is controlled by a SIR2 gene | journal = The EMBO Journal | volume = 18 | issue = 9 | pages = 2580–2592 | date = May 1999 | pmid = 10228170 | pmc = 1171338 | doi = 10.1093/emboj/18.9.2580 }}</ref><ref>{{cite book | vauthors = Dean L, McEntyre J | chapter = How Candida albicans switches phenotype - and back again | date = 24 November 1999 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK2316/ | title = Coffee Break: Tutorials for NCBI Tools | publisher = National Center for Biotechnology Information (US) | language = en | access-date = 7 January 2020 | archive-date = 8 July 2022 | archive-url = https://web.archive.org/web/20220708140134/https://www.ncbi.nlm.nih.gov/books/NBK2316/ | url-status = live }}</ref> ''SIR2'' was originally found in ''[[Saccharomyces cerevisiae]]'' (brewer's yeast), where it is involved in [[Gene silencing|chromosomal silencing]]—a form of [[transcriptional regulation]], in which regions of the [[genome]] are reversibly inactivated by changes in [[chromatin]] structure (chromatin is the complex of [[DNA]] and proteins that make [[chromosome]]s). In yeast, genes involved in the control of mating type are found in these silent regions, and ''SIR2'' represses their expression by maintaining a silent-competent chromatin structure in this region.<ref>{{cite web|url=https://www.yeastgenome.org/locus/S000002200|title=SIR2 {{pipe}} SGD|website=www.yeastgenome.org|access-date=2020-01-07|archive-date=2023-11-18|archive-url=https://web.archive.org/web/20231118161523/https://www.yeastgenome.org/locus/S000002200|url-status=live}}</ref> The discovery of a ''C. albicans SIR2'' implicated in phenotypic switching suggests it, too, has silent regions controlled by ''SIR2'', in which the phenotype-specific genes may reside. How ''SIR2'' itself is regulated in ''S. cerevisiae'' may yet provide more clues as to the switching mechanisms of ''C. albicans''.{{citation needed|date=August 2022}}

===White-opaque switching===

Next to the [[sexual dimorphism|dimorphism]] and the first described high-frequency switching system ''C. albicans'' undergoes another high-frequency switching process called white-opaque switching, which is another [[phenotypic switching]] process in ''C. albicans''. It was the second high-frequency switching system discovered in ''C. albicans''.<ref name="auto"/> The white-opaque switch is an [[Epigenetics|epigenetic]] switching system.<ref name="ReferenceA">{{cite journal | vauthors = Rikkerink EH, Magee BB, Magee PT | title = Opaque-white phenotype transition: a programmed morphological transition in Candida albicans | journal = Journal of Bacteriology | volume = 170 | issue = 2 | pages = 895–899 | date = February 1988 | pmid = 2828333 | pmc = 210739 | doi = 10.1128/jb.170.2.895-899.1988 }}</ref> Phenotypic switching is often used to refer to white-opaque switching, which consists of two phases: one that grows as round cells in smooth, white colonies (referred to as white form) and one that is rod-like and grows as flat, gray colonies (called opaque form). This switch between white cells and opaque cells is important for the virulence and the [[mating of yeast|mating]] process of ''C. albicans'' as the opaque form is the [[mating in fungi|mating]] competent form, being a million times more efficient in mating compared to the white type.<ref name="ReferenceA"/><ref>{{cite journal | vauthors = Lohse MB, Johnson AD | title = White-opaque switching in Candida albicans | journal = Current Opinion in Microbiology | volume = 12 | issue = 6 | pages = 650–654 | date = December 2009 | pmid = 19853498 | pmc = 2812476 | doi = 10.1016/j.mib.2009.09.010 }}</ref><ref>{{cite book |vauthors=Hnisz D, Tscherner M, Kuchler K |title=Yeast Genetic Networks |chapter=Morphological and Molecular Genetic Analysis of Epigenetic Switching of the Human Fungal Pathogen Candida albicans |volume=734 |issue=2 |pages=303–315 |year=2011 |doi=10.1007/978-1-61779-086-7_15|pmid=21468996|series=Methods in Molecular Biology |isbn=978-1-61779-085-0}}</ref> This switching between white and opaque form is regulated by the WOR1 regulator (White to Opaque Regulator 1) which is controlled by the [[mating type]] locus (MTL) repressor (a1-α2) that inhibits the expression of WOR1.<ref>{{cite journal | vauthors = Morschhäuser J | title = Regulation of white-opaque switching in Candida albicans | journal = Medical Microbiology and Immunology | volume = 199 | issue = 3 | pages = 165–172 | date = August 2010 | pmid = 20390300 | doi = 10.1007/s00430-010-0147-0 | s2cid = 8770123 }}</ref> Besides the white and opaque phase there is also a third one: the gray phenotype. This phenotype shows the highest ability to cause cutaneous infections. The white, opaque, and gray phenotypes form a phenotypic switching system where white cells switch to and from the opaque phase, white cells can irreversibly switch to the gray phase, and both white and gray cells can switch to and from the opaque/an opaque-like phase, respectively.<ref name="ReferenceC">{{cite journal | vauthors = Tao L, Du H, Guan G, Dai Y, Nobile CJ, Liang W, Cao C, Zhang Q, Zhong J, Huang G | display-authors = 6 | title = Discovery of a "white-gray-opaque" tristable phenotypic switching system in candida albicans: roles of non-genetic diversity in host adaptation | journal = PLOS Biology | volume = 12 | issue = 4 | pages = e1001830 | date = April 2014 | pmid = 24691005 | pmc = 3972085 | doi = 10.1371/journal.pbio.1001830 | doi-access = free }}</ref><ref name="Hemizygosity enables a mutational t">{{cite journal | vauthors = SLiang SH, Anderson MZ, Hirakawa MP, Wang JM, Frazer C, Alaalm LM, Thomson GJ, Ene IV, Bennett RJ | title = Hemizygosity enables a mutational transition governing fungal virulence and commensalism | journal = Cell Host Microbe | volume = 25 | issue = 3 | pages = 418–431.e6 | date = March 2019 | pmid = 30824263 | pmc = 6624852 | doi = 10.1016/j.chom.2019.01.005 }}</ref> Since it is often difficult to differentiate between white, opaque and gray cells phloxine B, a dye, can be added to the medium.<ref name="ReferenceC"/>

A potential regulatory molecule in the white to opaque switching is ''Efg1p'', a [[transcription factor]] found in the WO-1 strain that regulates dimorphism, and more recently has been suggested to help regulate phenotypic switching. ''Efg1p'' is expressed only in the white and not in the gray cell-type, and overexpression of ''Efg1p'' in the gray form causes a rapid conversion to the white form.<ref>{{cite journal | vauthors = Sonneborn A, Tebarth B, Ernst JF | title = Control of white-opaque phenotypic switching in Candida albicans by the Efg1p morphogenetic regulator | journal = Infection and Immunity | volume = 67 | issue = 9 | pages = 4655–4660 | date = September 1999 | pmid = 10456912 | pmc = 96790 | doi = 10.1128/IAI.67.9.4655-4660.1999 }}</ref><ref>{{cite journal | vauthors = Srikantha T, Tsai LK, Daniels K, Soll DR | title = EFG1 null mutants of Candida albicans switch but cannot express the complete phenotype of white-phase budding cells | journal = Journal of Bacteriology | volume = 182 | issue = 6 | pages = 1580–1591 | date = March 2000 | pmid = 10692363 | pmc = 94455 | doi = 10.1128/JB.182.6.1580-1591.2000 }}</ref><ref name="Hemizygosity enables a mutational t"/>

===Environmental stress===

Glucose starvation is a likely common environmental stress encountered by ''C. albicans'' in its natural habitat.<ref name="Guan2019">{{cite journal | vauthors = Guan G, Tao L, Yue H, Liang W, Gong J, Bing J, Zheng Q, Veri AO, Fan S, Robbins N, Cowen LE, Huang G | display-authors = 6 | title = Environment-induced same-sex mating in the yeast Candida albicans through the Hsf1-Hsp90 pathway | journal = PLOS Biology | volume = 17 | issue = 3 | pages = e2006966 | date = March 2019 | pmid = 30865631 | pmc = 6415874 | doi = 10.1371/journal.pbio.2006966 | doi-access = free }}</ref>  Glucose starvation causes an increase in [[reactive oxygen species|intracellular reactive oxygen]]. This stress can lead to mating between two individuals of the same mating type, an interaction that may be frequent in nature under stressful conditions.<ref name = Guan2019/>

===White-GUT switch===
A very special type of phenotypic switch is the white-GUT switch (Gastrointestinally-IndUced Transition). GUT cells are extremely adapted to survival in the digestive tract by metabolic adaptations to available nutrients in the digestive tract. The GUT cells live as commensal organisms and outcompete other phenotypes. The transition from white to GUT cells is driven by passage through the gut where environmental parameters trigger this transition by increasing the WOR1 expression.<ref>{{cite journal | vauthors = Pande K, Chen C, Noble SM | title = Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism | journal = Nature Genetics | volume = 45 | issue = 9 | pages = 1088–1091 | date = September 2013 | pmid = 23892606 | pmc = 3758371 | doi = 10.1038/ng.2710 }}</ref><ref>{{cite journal | vauthors = Noble SM, Gianetti BA, Witchley JN | title = Candida albicans cell-type switching and functional plasticity in the mammalian host | journal = Nature Reviews. Microbiology | volume = 15 | issue = 2 | pages = 96–108 | date = February 2017 | pmid = 27867199 | pmc = 5957277 | doi = 10.1038/nrmicro.2016.157 }}</ref>

==Role in disease==
{{Main|Candidiasis}}
''Candida'' is found worldwide but most commonly compromises immunocompromised individuals diagnosed with serious diseases such as HIV and cancer. ''Candida'' are ranked as one of the most common groups of organisms that cause [[hospital-acquired infection]]s. Especially high-risk individuals are patients that have recently undergone surgery, a transplant or are in the Intensive Care Units (ICU),<ref name=":0">{{cite web |url=https://microbewiki.kenyon.edu/index.php/Candida_albicans |title=Candida Albicans |vauthors=Brosnahan M |date=July 22, 2013 |website=MicrobeWiki |publisher=Kenyon College |access-date=October 24, 2016 |archive-date=November 18, 2023 |archive-url=https://web.archive.org/web/20231118161321/https://microbewiki.kenyon.edu/index.php/Candida_albicans |url-status=live }}</ref> ''C. albicans'' infections is the top source of fungal infections in critically ill or otherwise immunocompromised patients.<ref>{{cite journal | vauthors = Sydnor ER, Perl TM | title = Hospital epidemiology and infection control in acute-care settings | journal = Clinical Microbiology Reviews | volume = 24 | issue = 1 | pages = 141–173 | date = January 2011 | pmid = 21233510 | pmc = 3021207 | doi = 10.1128/CMR.00027-10 }}</ref> These patients predominantly develop oropharyngeal or thrush candidiasis, which can lead to malnutrition and interfere with the absorption of medication.<ref>{{cite journal | vauthors = Sardi JC, Scorzoni L, Bernardi T, Fusco-Almeida AM, Mendes Giannini MJ | title = Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options | journal = Journal of Medical Microbiology | volume = 62 | issue = Pt 1 | pages = 10–24 | date = January 2013 | pmid = 23180477 | doi = 10.1099/jmm.0.045054-0 | doi-access = free }}</ref> Methods of transmission include mother to infant through childbirth, people-to-people acquired infections that most commonly occur in hospital settings where immunocompromised patients acquire the yeast from healthcare workers and has a 40% incident rate.{{citation needed|date=November 2020}} People can become infected after having sex with a woman that has an existing vaginal yeast infection.<ref name=":0"/> Parts of the body that are commonly infected include the skin, genitals, throat, mouth, and blood.<ref>Tortora, Funke, Case. Microbiology, An Introduction 10th Edition. Pearson Benjamin Cummings. 2004, 2007, 2010.</ref> Distinguishing features of vaginal infection include discharge, and dry and red appearance of vaginal mucosa or skin. ''Candida'' continues to be the fourth most commonly isolated organism in bloodstream infections.<ref>{{cite web |url=http://www.medscape.org/viewarticle/462510 |title=Epidemiology, Management, and Prevention of Invasive Candidiasis |vauthors=Vazquez J |date=2016-04-16 |website=Medscape.org |publisher=Medscape |access-date=2016-04-16 |archive-date=2014-03-08 |archive-url=https://web.archive.org/web/20140308025902/http://www.medscape.org/viewarticle/462510 |url-status=live }}</ref> Healthy people usually do not suffer (severely) from superficial infections caused by a local alteration in cellular immunity as seen by asthma patients that use oral corticosteroids.{{Citation needed|date=January 2021}}

===Superficial and local infections===

It commonly occurs as a [[mycosis|superficial infection]] on mucous membranes in the [[oral candidiasis|mouth]] or vagina. Once in their lives around 75% of women will suffer from [[vaginal yeast infection|vulvovaginal candidiasis (VVC)]] and about 90% of these infections are caused by ''C. albicans''.{{citation needed|date=February 2021}} It may also affect a [[candidiasis#Classification|number of other regions]]. For example, higher [[prevalence]] of [[colonisation (biology)|colonization]] of ''C. albicans'' was reported in young individuals with [[tongue piercing]], in comparison to unpierced matched individuals,<ref name="Candida">{{cite journal | vauthors = Zadik Y, Burnstein S, Derazne E, Sandler V, Ianculovici C, Halperin T | title = Colonization of Candida: prevalence among tongue-pierced and non-pierced immunocompetent adults | journal = Oral Diseases | volume = 16 | issue = 2 | pages = 172–175 | date = March 2010 | pmid = 19732353 | doi = 10.1111/j.1601-0825.2009.01618.x | doi-access = free }}</ref> but not in healthy young individuals who use intraoral orthodontic acrylic appliances.<ref name="ORTHO">{{cite journal | vauthors = Yitschaky O, Katorza A, Zini A, Yitschaky M, Zadik Y | title = Acrylic orthodontic retainer is not a risk factor for focal Candida colonization in young healthy patients: a pilot study | journal =  Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology| volume = 121 | issue = 1 | pages = 39–42 | date = January 2016 | pmid = 26679358 | doi = 10.1016/j.oooo.2015.10.001 }}</ref> To infect host tissue, the usual [[unicellular organism|unicellular]] yeast-like form of ''C. albicans'' reacts to environmental cues and switches into an invasive, multicellular filamentous form, a phenomenon called [[Dimorphic fungus|dimorphism]].<ref name=Sherris>{{cite book |veditors=Ryan KJ, Ray CG |title=Sherris Medical Microbiology |edition=4th |publisher=McGraw Hill |year=2004 |isbn=978-0-8385-8529-0}}</ref> In addition, an overgrowth infection is considered a superinfection, the term usually applied when an infection becomes opportunistic and very [[Antimicrobial resistance|resistant]] to [[antifungal]]s. It then becomes suppressible by antibiotics{{clarify|date=July 2020 |reason=please clarify antifungal vs antibiotic vs antibacterial, and "then becomes suppressible" vs need another method of treatment}}{{Citation needed|reason=this info not present in the existing citations|date=July 2020}}. The infection is prolonged when the original sensitive strain is replaced by the antifungal-resistant strain.<ref>{{cite book |title=Microbiology: an Introduction |url=https://archive.org/details/microbiologyintr00tort_505 |url-access=limited | vauthors = Tortora GJ |publisher=Pearson Benjamin Cummings |year=2010 |location=San Francisco, CA |pages=[https://archive.org/details/microbiologyintr00tort_505/page/n791 759]}}</ref>

Candidiasis is known to cause gastrointestinal (GI) symptoms particularly in immunocompromised patients or those receiving steroids (e.g. to treat [[asthma]]) or antibiotics. Recently, there is an emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. Small intestinal fungal overgrowth (SIFO) is characterized by the presence of an excessive number of fungal organisms in the small intestine associated with gastrointestinal symptoms. The most common symptoms observed in these patients were belching, bloating, indigestion, nausea, diarrhea, and gas. The underlying mechanism(s) that predisposes to SIFO is unclear. Further studies are needed; both to confirm these observations and to examine the clinical relevance of fungal overgrowth.<ref name="SIFO"/><ref name="pmid24789109">{{cite journal | vauthors = Martins N, Ferreira IC, Barros L, Silva S, Henriques M | title = Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment | journal = Mycopathologia | volume = 177 | issue = 5–6 | pages = 223–240 | date = June 2014 | pmid = 24789109 | doi = 10.1007/s11046-014-9749-1 | hdl-access = free | quote = Candida species and other microorganisms are involved in this complicated fungal infection, but Candida albicans continues to be the most prevalent. In the past two decades, it has been observed that abnormal overgrowth in the gastrointestinal, urinary and respiratory tracts, not only in immunocompromised patients, but also related to nosocomial infections and even in healthy individuals. There is a wide variety of causal factors that contribute to yeast infection which means that candidiasis is a good example of a multifactorial syndrome. | s2cid = 795450 | hdl = 10198/10147 }}</ref><ref name="pmid25385227">{{cite journal | vauthors = Mukherjee PK, Sendid B, Hoarau G, Colombel JF, Poulain D, Ghannoum MA | title = Mycobiota in gastrointestinal diseases | journal = Nature Reviews. Gastroenterology & Hepatology | volume = 12 | issue = 2 | pages = 77–87 | date = February 2015 | pmid = 25385227 | doi = 10.1038/nrgastro.2014.188 | s2cid = 5370536 }}</ref>

===Systemic infections===

Systemic fungal infections ([[fungemia]]s) including those by ''C. albicans'' have emerged as important causes of [[morbidity]] and [[death|mortality]] in [[immunodeficiency|immunocompromised]] patients (e.g., [[HIV/AIDS|AIDS]], cancer [[chemotherapy]], organ or [[bone marrow]] transplantation). ''C. albicans'' often forms biofilms inside the body. Such ''C. albicans'' [[biofilm]]s may form on the surface of implantable medical devices or organs. In these biofilms it is often found together with ''[[Staphylococcus aureus]]''.<ref name="Kumamoto2002"/><ref name="Donlan2001"/><ref>{{cite journal | vauthors = Peters BM, Jabra-Rizk MA, Scheper MA, Leid JG, Costerton JW, Shirtliff ME | title = Microbial interactions and differential protein expression in Staphylococcus aureus -Candida albicans dual-species biofilms | journal = FEMS Immunology and Medical Microbiology | volume = 59 | issue = 3 | pages = 493–503 | date = August 2010 | pmid = 20608978 | pmc = 2936118 | doi = 10.1111/j.1574-695X.2010.00710.x }}</ref><ref>{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | display-authors = 6 | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 30–39 | year = 2013 | pmid = 32166015 | doi = 10.1893/0005-3155-84.1.30 | pmc = 7052475 | s2cid = 96930404 }}</ref> Such multispecies infections lead to higher mortalities.<ref>{{cite journal | vauthors = Zago CE, Silva S, Sanitá PV, Barbugli PA, Dias CM, Lordello VB, Vergani CE | title = Dynamics of biofilm formation and the interaction between Candida albicans and methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) | journal = PLOS ONE | volume = 10 | issue = 4 | pages = e0123206 | year = 2015 | pmid = 25875834 | pmc = 4395328 | doi = 10.1371/journal.pone.0123206 | doi-access = free | bibcode = 2015PLoSO..1023206Z }}</ref> In addition [[nosocomial infection|hospital-acquired infections]] by ''C. albicans'' have become a cause of major health concerns.<ref name=Calderone/><ref>{{cite book |title=Mibrobiology:an Introduction | vauthors = Tortora GJ |publisher=Pearson Benjamin Cummings |year=2010 |location=San Francisco, CA |pages=758}}</ref> Especially once candida cells are introduced in the bloodstream a high mortality, up to 40–60% can occur.<ref name=Calderone>{{cite book |veditors=Calderone A, Clancy CJ |title=Candida and Candidiasis |edition=2nd |publisher=ASM Press |year=2012 |isbn=978-1-55581-539-4}}</ref><ref>{{cite journal | vauthors = Weinberger M, Leibovici L, Perez S, Samra Z, Ostfeld I, Levi I, Bash E, Turner D, Goldschmied-Reouven A, Regev-Yochay G, Pitlik SD, Keller N | display-authors = 6 | title = Characteristics of candidaemia with Candida-albicans compared with non-albicans Candida species and predictors of mortality | journal = The Journal of Hospital Infection | volume = 61 | issue = 2 | pages = 146–154 | date = October 2005 | pmid = 16009456 | doi = 10.1016/j.jhin.2005.02.009 }}</ref>

Although ''Candida albicans'' is the most common cause of [[fungemia|candidemia]], there has been a decrease in the incidence and an increased isolation of non-albicans species of ''Candida'' in recent years.<ref>{{cite journal | vauthors = Yapar N | title = Epidemiology and risk factors for invasive candidiasis | journal = Therapeutics and Clinical Risk Management | volume = 10 | pages = 95–105 | date = 2016-04-16 | pmid = 24611015 | pmc = 3928396 | doi = 10.2147/TCRM.S40160 | doi-access = free }}</ref> Preventive measures include maintaining a good oral hygiene, keeping a healthy lifestyle including good nutrition, the careful use of antibiotics, treatment of infected areas and keeping skin dry and clean, free from open wounds.<ref>"Fungal Diseases." Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 12 June 2015, www.cdc.gov/fungal/diseases/candidiasis/invasive/diagnosis.html.</ref><ref>{{cite web|url=http://www.microbiologybook.org/mycology/mycology-3.htm|title=Yeasts|website=www.microbiologybook.org|access-date=27 March 2018|archive-date=14 March 2018|archive-url=https://web.archive.org/web/20180314095810/http://www.microbiologybook.org/mycology/mycology-3.htm|url-status=live}}</ref>

===Role of ''C. albicans'' in Crohn's disease===
The link between ''C. albicans'' and [[Crohn's disease]] has been investigated in a large cohort. This study demonstrated that members of families with multiple cases of Crohn's disease were more likely to be colonized by ''C. albicans'' than members of control families.<ref>{{cite journal | vauthors = Poulain D, Sendid B, Standaert-Vitse A, Fradin C, Jouault T, Jawhara S, Colombel JF | title = Yeasts: neglected pathogens | journal = Digestive Diseases | volume = 27 | issue = Suppl 1 | pages = 104–110 | date = 2009 | pmid = 20203505 | doi = 10.1159/000268129 | s2cid = 9014160 }}</ref> Experimental studies show that chemically induced colitis promotes ''C. albicans'' colonization. In turn, ''C. albicans'' colonization generates anti-''Saccharomyces cerevisiae'' antibodies (ASCA), increases inflammation, histological scores and pro-inflammatory cytokine expression.<ref>{{cite journal | vauthors = Jawhara S, Poulain D | title = Saccharomyces boulardii decreases inflammation and intestinal colonization by Candida albicans in a mouse model of chemically-induced colitis | journal = Medical Mycology | volume = 45 | issue = 8 | pages = 691–700 | date = December 2007 | pmid = 17885943 | doi = 10.1080/13693780701523013 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Jawhara S, Thuru X, Standaert-Vitse A, Jouault T, Mordon S, Sendid B, Desreumaux P, Poulain D | display-authors = 6 | title = Colonization of mice by Candida albicans is promoted by chemically induced colitis and augments inflammatory responses through galectin-3 | journal = The Journal of Infectious Diseases | volume = 197 | issue = 7 | pages = 972–980 | date = April 2008 | pmid = 18419533 | doi = 10.1086/528990 | doi-access = free }}</ref>

===Diagnosis===
A United States study in 2022 showed that most cases of candidiasis are treated [[empiric therapy|empirically]] (without culture, pending culture or by symptoms in cases where culture did not show candida), thus not knowing whether the subtype is ''Candida albicans'' or any other candida species.<ref name="pmid36505943">{{cite journal| author=Eguiguren L, Lee BR, Newland JG, Kronman MP, Hersh AL, Gerber JS | display-authors=etal| title=Characteristics of antifungal utilization for hospitalized children in the United States. | journal=Antimicrob Steward Healthc Epidemiol | year= 2022 | volume= 2 | issue= 1 | pages= e190 | pmid=36505943 | doi=10.1017/ash.2022.338 | pmc=9726632 }}</ref> For subtyping of candidiasis, a [[fungal culture]] can be performed, followed by a [[germ tube]] test in which a sample of fungal spores are suspended in animal [[blood serum|serum]] and examined by [[microscopy]] for the detection of any germ tubes.<ref name=doctorfungus>Chapter  IV. Germ Tube Test in [http://www.doctorfungus.org/thelabor/sec12.pdf YEAST IDENTIFICATION] {{Webarchive|url=https://web.archive.org/web/20110927045233/http://www.doctorfungus.org/thelabor/sec12.pdf |date=2011-09-27 }} document at doctorfungus.org. Retrieved July 2011</ref> Colonies of white or cream color on fungal culture having a positive germ tube test is strongly indicative of ''Candida albicans''.<ref name=doctorfungus/>
<gallery>
File:Candida albicans PHIL 3192 lores.jpg|[[Agar plate]] culture of ''C. albicans''
File:C albicans germ tubes.jpg|Germ tubes of ''Candida albicans''
File:Candida Gram stain.jpg|[[Gram stain]] of ''Candida albicans'' from a vaginal swab; the small oval [[chlamydospore]]s are 2–4&nbsp;[[micrometre|μm]] in diameter 
File:CHROMAgar with N glabratus, P kudriavzevii, Candida albicans and Candida tropicalis, annotated.jpg|Chromogenic agar can help in indicating main species of ''Candida'' versus similar fungi. (CHROMAgar shown)
File:Mycology algorithm.png|Algorithm for the diagnosis of ''Candida albicans'' versus differential diagnoses
</gallery>

===Treatment===
There are relatively few drugs that can successfully treat Candidiasis.<ref name="Sellama">{{cite journal | vauthors = Sellam A, Whiteway M | title = Recent advances on ''Candida albicans'' biology and virulence | journal = F1000Research | volume = 5 | pages = 2582 | date = 2016 | pmid = 27853524 | pmc = 5089126 | doi = 10.12688/f1000research.9617.1 | doi-access = free }}</ref><ref>{{cite journal | vauthors =  | title = Stop neglecting fungi | journal = Nature Microbiology | volume = 2 | issue = 8 | pages = 17120 | date = July 2017 | pmid = 28741610 | doi = 10.1038/nmicrobiol.2017.120 | doi-access = free }}</ref> Treatment commonly includes:<ref>{{cite journal | vauthors = Rambach G, Oberhauser H, Speth C, Lass-Flörl C | title = Susceptibility of Candida species and various moulds to antimycotic drugs: use of epidemiological cutoff values according to EUCAST and CLSI in an 8-year survey | journal = Medical Mycology | volume = 49 | issue = 8 | pages = 856–863 | date = November 2011 | pmid = 21619497 | doi = 10.3109/13693786.2011.583943 | doi-access = free }}</ref>
* [[amphotericin B]], [[echinocandin]], or [[fluconazole]] for systemic infections
* [[nystatin]] for oral and esophageal infections
* [[clotrimazole]] for skin and genital yeast infections<ref>{{cite book | vauthors =  Tortora GJ, Funke BR, Case CL  |title= Microbiology an Introduction |year=2002 |url=https://archive.org/details/microbiologyintr00gera |url-access=limited |publisher=Pearson Benjamin Cummings |location=San Francisco, CA. |pages=[https://archive.org/details/microbiologyintr00gera/page/759 759] |edition=10th}}</ref>
Similarly to antibiotic resistance, resistance to many anti-fungals is becoming a problem. New anti-fungals have to be developed to cope with this problem since only a limited number of anti-fungals are available.<ref name="Sellama"/><ref>{{cite web|url=https://www.cdc.gov/fungal/antifungal-resistance.html|title=Antifungal Resistance – Fungal Diseases – CDC|date=26 June 2017|website=www.cdc.gov|access-date=27 March 2018|archive-date=19 May 2017|archive-url=https://web.archive.org/web/20170519094753/https://www.cdc.gov/fungal/antifungal-resistance.html|url-status=live}}</ref> A general problem is that in contrast to bacteria, fungi are often overlooked as a potential health problem.<ref>{{cite journal | vauthors =  | title = Stop neglecting fungi | journal = Nature Microbiology | volume = 2 | issue = 8 | pages = 17120 | date = July 2017 | pmid = 28741610 | doi = 10.1038/nmicrobiol.2017.120 | doi-access = free | department = Editorial }}</ref>

===Economic implications===
Given the fact that candidiasis is the fourth- (to third-) most frequent hospital acquired infection worldwide it leads to immense financial implications. Approximately 60,000 cases of systemic candidiasis each year in the USA alone lead up to a cost to be between $2–4 billion.<ref>{{cite book| vauthors = Uppuluri P, Khan A, Edwards JE | veditors = Prasad R |title=Candida albicans: Cellular and Molecular Biology|date=2017|publisher=Springer International Publishing AG|location=Switzerland|isbn=978-3-319-50408-7|page=6|chapter=Current Trends in Candidiasis}}</ref> The total costs for candidiasis are among the highest compared to other fungal infections due to the high prevalence.<ref>{{cite journal | vauthors = Wilson LS, Reyes CM, Stolpman M, Speckman J, Allen K, Beney J | title = The direct cost and incidence of systemic fungal infections | journal = Value in Health | volume = 5 | issue = 1 | pages = 26–34 | year = 2002 | pmid = 11873380 | doi = 10.1046/j.1524-4733.2002.51108.x | doi-access = free }}</ref> The immense costs are partly explained by a longer stay in the intensive care unit or hospital in general. An extended stay for up to 21 more days compared to non-infected patients is not uncommon.<ref>{{cite journal | vauthors = Rentz AM, Halpern MT, Bowden R | title = The impact of candidemia on length of hospital stay, outcome, and overall cost of illness | journal = Clinical Infectious Diseases | volume = 27 | issue = 4 | pages = 781–788 | date = October 1998 | pmid = 9798034 | doi = 10.1086/514955 | doi-access = free }}</ref>

=== Role of GSDMD in C.albicans infection ===
Gasdermin D (GSDMD) is a protein that in humans is encoded by the GSDMD gene and is a known target of the inflammasome and acts as an effector molecule of programmed cell death known as pyroptosis. This protein determines cell lysis to prevent pathogen replication and results in the release of the inflammatory cytokine interleukin-1β (IL-1β) into the extracellular space to recruit and activate immune cells at the site of infection. Inflammasome activation due to C.albicans infection triggers the release of a [[cytokine storm]] necessary to fight the pathogen. Excessive release of these pro-inflammatory mediators has been shown to exaggerate systemic inflammation leading to vascular injury and damage to vital organs. Unfortunately, Candida albicans therapy is often ineffective despite the availability of many antifungal drugs, mainly because of resistance phenomena. During conventional pyroptosis controlled by the inflammasome-GSDMD axis is hijacked by C. albicans to facilitate escape from macrophages through unfolding of hyphae and candidalysin, a fungal toxin released from hyphae. It has been shown<ref>{{cite journal |last1=Ding |first1=Xionghui |last2=Kambara |first2=Hiroto |last3=Guo |first3=Rongxia |last4=Kanneganti |first4=Apurva |last5=Acosta-Zaldívar |first5=Maikel |last6=Li |first6=Jiajia |last7=Liu |first7=Fei |last8=Bei |first8=Ting |last9=Qi |first9=Wanjun |last10=Xie |first10=Xuemei |last11=Han |first11=Wenli |last12=Liu |first12=Ningning |last13=Zhang |first13=Cunling |last14=Zhang |first14=Xiaoyu |last15=Yu |first15=Hongbo |date=2021-11-18 |title=Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages |journal=Nature Communications |volume=12 |issue=1 |pages=6699 |doi=10.1038/s41467-021-27034-9 |issn=2041-1723 |pmc=8602704 |pmid=34795266|bibcode=2021NatCo..12.6699D }}</ref> that disruption of GSDMD in macrophages infected with Candida albicans reduces the fungal load. In addition, the presence of hyphae and candidalysin are key factors in the activation of GSDMD and the release of Candida from macrophages. Also using Candida-infected mice, inhibition of GSDMD has been shown to paradoxically improve prognosis and survival, indicating that this protein may be a potential therapeutic target in C. albicans-induced sepsis.{{citation needed|date=March 2023}}

==Biofilm development==

===Biofilm formation steps===
The biofilm of ''C. albicans'' is formed in four steps. First, there is the initial adherence step, where the yeast-form cells adhere to the substrate. The second step is called Intermediate step, where the cells propagate to form [[Colony (biology)#Types|micro colonies]], and germ tubes form to yield hyphae. In the maturation step, the biofilm biomass expands, the extracellular matrix accumulates and drug resistance increases. In the last step of biofilm formation, the yeast-form cells are released to colonize the surrounding environment (dispersion). Yeast cells released from a biofilm have novel properties, including increased virulence and drug tolerance.<ref>{{cite journal | vauthors = McCall AD, Pathirana RU, Prabhakar A, Cullen PJ, Edgerton M | title = ''Candida albicans'' biofilm development is governed by cooperative attachment and adhesion maintenance proteins | journal = npj Biofilms and Microbiomes | volume = 5 | issue = 1 | pages = 21 | date = 23 August 2019 | pmid = 31452924 | pmc = 6707306 | doi = 10.1038/s41522-019-0094-5 }}</ref><ref>{{cite journal | vauthors = Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA | title = Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance | journal = Journal of Bacteriology | volume = 183 | issue = 18 | pages = 5385–5394 | date = September 2001 | pmid = 11514524 | pmc = 95423 | doi = 10.1128/jb.183.18.5385-5394.2001 }}</ref><ref>{{cite journal | vauthors = Gulati M, Nobile CJ | title = Candida albicans biofilms: development, regulation, and molecular mechanisms | journal = Microbes and Infection | volume = 18 | issue = 5 | pages = 310–321 | date = May 2016 | pmid = 26806384 | pmc = 4860025 | doi = 10.1016/j.micinf.2016.01.002 }}</ref>

===Zap1===
Zap1, also known as Csr1 and Sur1 (zinc-responsive activator protein), is a transcription factor required for the ''C. albicans'' hypha formation in biofilms. Zap1 controls the equilibrium of yeast and hyphal cells, the zinc transporters and zinc regulated genes in biofilms of ''C. albicans''.<ref>{{cite journal | vauthors = Finkel JS, Mitchell AP | title = Genetic control of Candida albicans biofilm development | language = En | journal = Nature Reviews. Microbiology | volume = 9 | issue = 2 | pages = 109–118 | date = February 2011 | pmid = 21189476 | pmc = 3891587 | doi = 10.1038/nrmicro2475 }}</ref>
===Zinc===
Zinc (Zn<sup>2+</sup>) is important for cell function of ''C. albicans'' and Zap1 controls the Zinc levels in the cells through the zinc transporters Zrt1 and Zrt2. The regulation of zinc concentration in the cells is important for the cell viability and if the zinc levels get too high, it is toxic for the cells. The Zrt1 is transporting the zinc ions with high affinity and the Zrt2 is transporting the zinc ions with low affinity.<ref>{{cite journal | vauthors = Claus J, Chavarría-Krauser A | title = Modeling regulation of zinc uptake via ZIP transporters in yeast and plant roots | journal = PLOS ONE | volume = 7 | issue = 6 | pages = e37193 | date = 2012-06-08 | pmid = 22715365 | pmc = 3371047 | doi = 10.1371/journal.pone.0037193 | arxiv = 1202.4335 | doi-access = free | bibcode = 2012PLoSO...737193C }}</ref>

==Mechanisms and proteins important for pathogenesis==

===Filamentation===
The ability to switch between yeast cells and hyphal cells is an important virulence factor. Many proteins play a role in this  very complex process.<ref>{{cite journal | vauthors = Azadmanesh J, Gowen AM, Creger PE, Schafer ND, Blankenship JR | title = Filamentation Involves Two Overlapping, but Distinct, Programs of Filamentation in the Pathogenic Fungus ''Candida albicans'' | journal = G3 | volume = 7 | issue = 11 | pages = 3797–3808 | date = November 2017 | pmid = 28951491 | pmc = 5677161 | doi = 10.1534/g3.117.300224 }}</ref> The formation of hyphae can for example help ''Candida albicans'' to escape from macrophages in the human body.<ref>{{cite journal | vauthors = Lorenz MC, Bender JA, Fink GR | title = Transcriptional response of Candida albicans upon internalization by macrophages | journal = Eukaryotic Cell | volume = 3 | issue = 5 | pages = 1076–1087 | date = October 2004 | pmid = 15470236 | pmc = 522606 | doi = 10.1128/EC.3.5.1076-1087.2004 }}</ref> Moreover, ''C. albicans'' undergo yeast-to-hyphal transition within the acidic macrophage phagosome. This initially causes phagosome membrane distension which eventually leads to phagosomal alkalinization by physical rupture, followed by escape.<ref>{{cite journal | vauthors = Westman J, Moran G, Mogavero S, Hube B, Grinstein S | title = Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization | journal = mBio | volume = 9 | issue = 5 | pages = e01226–18 | date = September 2018 | pmid = 30206168 | pmc = 6134096 | doi = 10.1128/mBio.01226-18 }}</ref>

===Hwp1===
{{Main|Hwp1}}
Hwp1 stands for Hyphal wall protein 1. Hwp1 is a mannoprotein located on the surface of the hyphae in the hyphal form of ''C. albicans''. Hwp1 is a mammalian [[transglutaminase]] substrate. This host enzyme allows ''Candida albicans'' to [[fungal adhesin|attach]] stably to host epithelial cells.<ref name="Staab1999">{{cite journal | vauthors = Staab JF, Bradway SD, Fidel PL, Sundstrom P | title = Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1 | journal = Science | volume = 283 | issue = 5407 | pages = 1535–1538 | date = March 1999 | pmid = 10066176 | doi = 10.1126/science.283.5407.1535 | bibcode = 1999Sci...283.1535S }}</ref> Adhesion of ''C. albicans'' to host cells is an essential first step in the infection process for colonization and subsequent induction of mucosal infection.{{Citation needed|date=January 2021}}

===Slr1===
The [[RNA-binding protein]] Slr1 plays a role in instigating hyphal formation and virulence in ''C. albicans''.<ref name="AriyachetSolis2013">{{cite journal | vauthors = Ariyachet C, Solis NV, Liu Y, Prasadarao NV, Filler SG, McBride AE | title = SR-like RNA-binding protein Slr1 affects Candida albicans filamentation and virulence | journal = Infection and Immunity | volume = 81 | issue = 4 | pages = 1267–1276 | date = April 2013 | pmid = 23381995 | pmc = 3639594 | doi = 10.1128/IAI.00864-12 }}</ref>

===Candidalysin===
[[Candidalysin]] is a cytolytic 31-amino acid α-helical peptide toxin that is released by ''C. albicans'' during hyphal formation. It contributes to virulence during mucosal infections.<ref>{{cite journal | vauthors = Wilson D, Naglik JR, Hube B | title = The Missing Link between Candida albicans Hyphal Morphogenesis and Host Cell Damage | journal = PLOS Pathogens | volume = 12 | issue = 10 | pages = e1005867 | date = October 2016 | pmid = 27764260 | pmc = 5072684 | doi = 10.1371/journal.ppat.1005867 | doi-access = free }}</ref>

===PRA1===
During vaginal infections PRA1 (pH-regulated antigen) gene is up-regulated. Its expression correlates with the  concentration of [[proinflammatory cytokines]].<ref name="rose">{{Cite journal |last1=Roselletti |first1=Elena |last2=Pericolini |first2=Eva |last3=Nore |first3=Alexandre |last4=Takacs |first4=Peter |last5=Kozma |first5=Bence |last6=Sala |first6=Arianna |last7=De Seta |first7=Francesco |last8=Comar |first8=Manola |last9=Usher |first9=Jane |last10=Brown |first10=Gordon D. |last11=Wilson |first11=Duncan |date=2023-12-06 |title=Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein |journal=Science Translational Medicine |language=en |volume=15 |issue=725 |pages=eadi3363 |doi=10.1126/scitranslmed.adi3363 |pmid=38055800 |pmc=7616067 |issn=1946-6234|hdl=10871/134775 |hdl-access=free }}</ref> 
==Genetic and genomic tools==

Due to its nature as a model organism, being an important human pathogen and the alternative codon usage (CUG translated into serine rather than leucine), several specific projects and tools have been created to study ''C. albicans''.<ref name="Calderone"/> The diploid nature and the absence of a sexual cycle make the organism difficult to study, but in the last 20 years, many systems have been developed to observe its genetics.<ref name="Kabir"/>

===Selection markers===
The selection markers most used in ''C. albicans'' are the CaNAT1 resistance marker (confers resistance against [[nourseothricin]]) and MPAr or IMH3r (confers resistance to [[mycophenolic acid]]).<ref>{{cite journal | vauthors = Shen J, Guo W, Köhler JR | title = CaNAT1, a heterologous dominant selectable marker for transformation of Candida albicans and other pathogenic Candida species | journal = Infection and Immunity | volume = 73 | issue = 2 | pages = 1239–1242 | date = February 2005 | pmid = 15664973 | pmc = 547112 | doi = 10.1128/IAI.73.2.1239-1242.2005 }}</ref>
Next to the above-mentioned selection makers a few auxotrophic strains were generated to work with auxotrophic makers. The [[URA3]] marker (URA3 blaster method) is an often-used strategy in uridine auxotrophic strains; however, studies have shown that differences in URA3 position in the genome can be involved in the pathogeny of ''C. albicans''.<ref>{{cite journal | vauthors = Cheng S, Nguyen MH, Zhang Z, Jia H, Handfield M, Clancy CJ | title = Evaluation of the roles of four Candida albicans genes in virulence by using gene disruption strains that express URA3 from the native locus | journal = Infection and Immunity | volume = 71 | issue = 10 | pages = 6101–6103 | date = October 2003 | pmid = 14500538 | pmc = 201070 | doi = 10.1128/IAI.71.10.6101-6103.2003 }}</ref> Besides the URA3 selection one can also use the histidine, leucine and arginine autotrophy. The advantage of using those autotrophies lies in the fact that they exhibit wild-type or nearly wild-type virulence in a mouse model compared to the URA3 system.<ref>{{cite journal | vauthors = Noble SM, Johnson AD | title = Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans | journal = Eukaryotic Cell | volume = 4 | issue = 2 | pages = 298–309 | date = February 2005 | pmid = 15701792 | pmc = 549318 | doi = 10.1128/EC.4.2.298-309.2005 }}</ref> One application of the leucine, arginine and histidine autotrophy is for example the candida two-hybrid system.<ref name="stynen"/>

===Full sequence genome===

The full genome of ''C. albicans'' has been sequenced and made publicly available in a [http://www.candidagenome.org Candida database]. The heterozygous diploid strain used for this full genome sequence project is the laboratory strain SC5314. The sequencing was done using a whole-genome shotgun approach.<ref>{{cite journal | vauthors = van het Hoog M, Rast TJ, Martchenko M, Grindle S, Dignard D, Hogues H, Cuomo C, Berriman M, Scherer S, Magee BB, Whiteway M, Chibana H, Nantel A, Magee PT | display-authors = 6 | title = Assembly of the Candida albicans genome into sixteen supercontigs aligned on the eight chromosomes | journal = Genome Biology | volume = 8 | issue = 4 | pages = R52 | date = 2007 | pmid = 17419877 | pmc = 1896002 | doi = 10.1186/gb-2007-8-4-r52 | doi-access = free }}</ref>

===ORFeome project===

Every predicted ORF has been created in a gateway adapted vector (pDONR207) and made publicly available. The vectors ([[plasmid]]s) can be propagated in ''E.coli'' and grown on LB+[[gentamicin]] medium. This way every ORF is readily available in an easy to use vector. Using the gateway system it is possible to transfer the ORF of interest to any other gateway adapted vector for further studies of the specific ORF.<ref name="ReferenceB"/><ref>{{cite book | vauthors = Cabral V, Chauevl M, Firon A, Legrand M, Nesseir A, Bachellier-Bassi S, Chaudhari Y, Munro CA, d'Enfert C | chapter = Modular Gene Over-expression Strategies for Candida albicans | title = Host-Fungus Interactions | display-authors = 6 | series = Methods in Molecular Biology | volume = 845 | pages = 227–244 | year = 2012 | pmid = 22328378 | doi = 10.1007/978-1-61779-539-8_15 | isbn = 978-1-61779-538-1 | veditors = Brand AC, MacCallum DM }}</ref>

===CIp10 integrative plasmid===

Contrary to the yeast [[Saccharomyces cerevisiae|''S. cerevisiae'']] episomal plasmids do not stay stable in ''C. albicans''. In order to work with plasmids in ''C. albicans'' an integrative approach (plasmid integration into the genome) thus has to be used. A second problem is that most plasmid transformations are rather inefficient in ''C. albicans''; however, the CIp10 plasmid overcomes these problems and can be used with ease to transform ''C. albicans'' in a very efficient way. The plasmid integrates inside the RP10 locus as disruption of one RP10 allele does not seem to affect the viability and growth of ''C. albicans''. Several adaptations of this plasmid have been made after the original became available.<ref>{{cite journal | vauthors = Chauvel M, Nesseir A, Cabral V, Znaidi S, Goyard S, Bachellier-Bassi S, Firon A, Legrand M, Diogo D, Naulleau C, Rossignol T, d'Enfert C | display-authors = 6 | title = A versatile overexpression strategy in the pathogenic yeast Candida albicans: identification of regulators of morphogenesis and fitness | journal = PLOS ONE | volume = 7 | issue = 9 | pages = e45912 | year = 2012 | pmid = 23049891 | pmc = 3457969 | doi = 10.1371/journal.pone.0045912 | doi-access = free | bibcode = 2012PLoSO...745912C }}</ref><ref name="auto2">{{cite journal | vauthors = Walker LA, Maccallum DM, Bertram G, Gow NA, Odds FC, Brown AJ | title = Genome-wide analysis of Candida albicans gene expression patterns during infection of the mammalian kidney | journal = Fungal Genetics and Biology | volume = 46 | issue = 2 | pages = 210–219 | date = February 2009 | pmid = 19032986 | pmc = 2698078 | doi = 10.1016/j.fgb.2008.10.012 }}</ref>

===Candida two-hybrid (C2H) system===

Due to the aberrant codon usage of ''C. albicans'' it is less feasible to use the common host organism (''[[Saccharomyces cerevisiae]]'') for [[two-hybrid screening|two-hybrid studies]]. To overcome this problem a ''C. albicans'' two-hybrid (C2H) system was created. The strain SN152 that is auxotrophic for leucine, arginine and histidine was used to create this C2H system. It was adapted by integrating a HIS1 reporter gene preceded by five LexAOp sequences.
In the C2H system the bait plasmid (pC2HB) contains the ''[[Staphylococcus aureus]]'' LexA BD, while the prey plasmid (pC2HP) harbors the viral AD VP16. Both plasmids are integrative plasmids since episomal plasmids do not stay stable in ''C. albicans''. The reporter gene used in the system is the ''HIS1'' gene. When proteins interact, the cells will be able to grow on medium lacking histidine due to the activation of the ''HIS1'' reporter gene.<ref name="Calderone"/><ref name="stynen"/> Several interactions have thus far been detected using this system in a low scale set up.<ref name="stynen"/><ref>{{cite journal | vauthors = Legrand M, Bachellier-Bassi S, Lee KK, Chaudhari Y, Tournu H, Arbogast L, Boyer H, Chauvel M, Cabral V, Maufrais C, Nesseir A, Maslanka I, Permal E, Rossignol T, Walker LA, Zeidler U, Znaidi S, Schoeters F, Majgier C, Julien RA, Ma L, Tichit M, Bouchier C, Van Dijck P, Munro CA, d'Enfert C | display-authors = 6 | title = Generating genomic platforms to study Candida albicans pathogenesis | journal = Nucleic Acids Research | volume = 46 | issue = 14 | pages = 6935–6949 | date = August 2018 | pmid = 29982705 | pmc = 6101633 | doi = 10.1093/nar/gky594 }}</ref> A first high-throughput screening has also been performed.<ref>{{cite journal | vauthors = Schoeters F, Munro CA, d'Enfert C, Van Dijck P | title = A High-Throughput ''Candida albicans'' Two-Hybrid System | journal = mSphere | volume = 3 | issue = 4 | date = August 2018 | pmid = 30135223 | pmc = 6106057 | doi = 10.1128/mSphere.00391-18 }}</ref><ref name="frontiersin.org">{{cite journal | vauthors = Schoeters F, Van Dijck P | title = Protein-Protein Interactions in ''Candida albicans'' | journal = Frontiers in Microbiology | volume = 10 | pages = 1792 | date = 2019 | pmid = 31440220 | pmc = 6693483 | doi = 10.3389/fmicb.2019.01792 | doi-access = free }}</ref> Interacting proteins can be found at the [[BioGRID]].<ref>{{cite web|url=https://thebiogrid.org/|title=BioGRID - Database of Protein, Chemical, and Genetic Interactions|vauthors=Tyers M|website=thebiogrid.org|access-date=2018-08-25|archive-date=2017-09-11|archive-url=https://web.archive.org/web/20170911015109/https://thebiogrid.org/|url-status=live}}</ref>

===Bimolecular fluorescence complementation (BiFC)===

Besides the C2H system, a [[bimolecular fluorescence complementation|BiFC]] system has been developed to study protein-protein interactions in ''C. albicans''. With this systems protein interactions can be studied in their native sub cellular location contrary to a C2H system in which the proteins are forced into the nucleus. With BiFC one can study for example protein interactions that take place at the cell membrane or vacuolar membrane.<ref name="frontiersin.org"/><ref>{{cite journal | vauthors = Subotić A, Swinnen E, Demuyser L, De Keersmaecker H, Mizuno H, Tournu H, Van Dijck P | title = A Bimolecular Fluorescence Complementation Tool for Identification of Protein-Protein Interactions in ''Candida albicans'' | journal = G3 | volume = 7 | issue = 10 | pages = 3509–3520 | date = October 2017 | pmid = 28860184 | pmc = 5633398 | doi = 10.1534/g3.117.300149 }}</ref><ref>{{cite journal | vauthors = Mamouei Z, Zeng G, Wang YM, Wang Y | title = Candida albicans possess a highly versatile and dynamic high-affinity iron transport system important for its commensal-pathogenic lifestyle | journal = Molecular Microbiology | volume = 106 | issue = 6 | pages = 986–998 | date = December 2017 | pmid = 29030877 | doi = 10.1111/mmi.13864 | doi-access = free }}</ref>

===Microarrays===
Both DNA and protein microarrays were designed to study DNA expression profiles and antibody production in patients against ''C. albicans'' cell wall proteins.<ref name="auto2"/><ref>{{cite journal | vauthors = Mochon AB, Jin Y, Kayala MA, Wingard JR, Clancy CJ, Nguyen MH, Felgner P, Baldi P, Liu H | display-authors = 6 | title = Serological profiling of a Candida albicans protein microarray reveals permanent host-pathogen interplay and stage-specific responses during candidemia | journal = PLOS Pathogens | volume = 6 | issue = 3 | pages = e1000827 | date = March 2010 | pmid = 20361054 | pmc = 2845659 | doi = 10.1371/journal.ppat.1000827 | doi-access = free }}</ref>

===GRACE library===

Using a [[tetracycline-controlled transcriptional activation|tetracycline-regulatable promoter system]] a gene replacement and conditional expression (GRACE) library was created for 1,152 genes. By using the regulatable promoter and having deleted 1 of the alleles of the specific gene it was possible to discriminate between non-essential and essential genes. Of the tested 1,152 genes 567 showed to be essential. The knowledge on essential genes can be used to discover novel antifungals.<ref name="Large-scale essential gene identifi"/>

===CRISPR/Cas9===

[[CRISPR|CRISPR/Cas9]] has been adapted to be used in ''C. albicans''.<ref>{{cite journal | vauthors = Dean N, Ng H | title = Method for CRISPR/Cas9 Mutagenesis in ''Candida albicans'' | journal = Bio-Protocol | volume = 8 | issue = 8 | pages = e2814 | date = April 2018 | pmid = 34286028 | pmc = 8275232 | doi = 10.21769/BioProtoc.2814 | s2cid = 90620202 }}</ref> Several studies have been performed using this system.<ref>{{cite journal | vauthors = Vyas VK, Barrasa MI, Fink GR | title = A ''Candida albicans'' CRISPR system permits genetic engineering of essential genes and gene families | journal = Science Advances | volume = 1 | issue = 3 | pages = e1500248 | year = 2015 | pmid = 25977940 | pmc = 4428347 | doi = 10.1126/sciadv.1500248 | bibcode = 2015SciA....1E0248V }}</ref><ref>{{cite journal | vauthors = Min K, Ichikawa Y, Woolford CA, Mitchell AP | title = Candida albicans Gene Deletion with a Transient CRISPR-Cas9 System | journal = mSphere | volume = 1 | issue = 3 | year = 2016 | pmid = 27340698 | pmc = 4911798 | doi = 10.1128/mSphere.00130-16 }}</ref>

==Application in engineering==
''C. albicans'' has been used in combination with carbon nanotubes (CNT) to produce stable electrically conductive bio-nano-composite tissue materials that have been used as temperature-sensing elements.<ref>{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | display-authors = 6 | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 111–114 | year = 2013 | pmid = 32166015 | doi = 10.1109/TNANO.2013.2239308 | pmc = 7052475 | s2cid = 26949825 | bibcode = 2013ITNan..12..111D }}</ref>

==Notable ''C. albicans'' researchers==
* [[Neil A. R. Gow]]
* [[Alexander D. Johnson]]
* [[Frank Odds|Frank C. Odds]]
* [[Charles Philippe Robin]]
* [[Fred Sherman (scientist)|Fred Sherman]]
* [[David R. Soll]]

== See also ==
{{Portal|Fungi}}
* [[Intestinal permeability]]
* [[Torula|Torula yeast]] (''Candida utilis'')
* [[Neonatal infection]]
* [[Codon usage]]

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite book | vauthors = Odds FC |title=Candida and candidosis |date=1988 |publisher=Baillière Tindall |isbn=978-0702012655 |edition=2nd}}
* {{cite journal | vauthors = Waldman A, Gilhar A, Duek L, Berdicevsky I | title = Incidence of Candida in psoriasis--a study on the fungal flora of psoriatic patients | journal = Mycoses | volume = 44 | issue = 3–4 | pages = 77–81 | date = May 2001 | pmid = 11413927 | doi = 10.1046/j.1439-0507.2001.00608.x | s2cid = 36201859 }}
* {{cite journal | vauthors = Zordan RE, Miller MG, Galgoczy DJ, Tuch BB, Johnson AD | title = Interlocking transcriptional feedback loops control white-opaque switching in Candida albicans | journal = PLOS Biology | volume = 5 | issue = 10 | pages = e256 | date = October 2007 | pmid = 17880264 | pmc = 1976629 | doi = 10.1371/journal.pbio.0050256 | doi-access = free }}
* {{cite journal | vauthors = Rossignol T, Lechat P, Cuomo C, Zeng Q, Moszer I, d'Enfert C | title = CandidaDB: a multi-genome database for Candida species and related Saccharomycotina | journal = Nucleic Acids Research | volume = 36 | issue = Database issue | pages = D557–D561 | date = January 2008 | pmid = 18039716 | pmc = 2238939 | doi = 10.1093/nar/gkm1010 }}
* {{cite web |url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=coffeebrk.chapter.20 |title=How Candida albicans switches phenotype&nbsp;– and back again: the SIR2 silencing gene has a say in Candida's colony type |work=NCBI Coffeebreak |date=1999-11-24 |access-date=2008-11-02}}
{{refend}}

== External links ==
{{Commons}}
* [http://www.candidagenome.org/ ''Candida'' Genome Database]
* [https://web.archive.org/web/20041028100712/http://www.ncbi.nih.gov/mapview/map_search.cgi?taxid=5476 U.S. National Institutes of Health on the ''Candida albicans'' genome]
* [http://www.mycobank.org/name/Candida%20albicans Mycobank data on ''Candida albicans'']
* [http://www.candidagenome.org/cache/Labs.html Labs working on Candida]
* [https://thebiogrid.org Protein-protein interactions for Candida albicans]

{{Mycoses}}

{{Taxonbar|from=Q310443}}
{{Authority control}}

[[Category:Candida (fungus)|albicans]]
[[Category:Gut flora]]
[[Category:Organisms with an alternative genetic code]]
[[Category:Pathogenic microbes]]
[[Category:Fungal pathogens of humans]]
[[Category:Yeasts]]
[[Category:Fungi described in 1923]]
[[Category:Fungus species]]