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Candida albicans
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===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}}
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