Editing Mycobacterium

{{Short description|Genus of bacteria}}
{{Good article}}
{{Automatic taxobox
| image = Mycobacterium tuberculosis 01.jpg
| image_caption = [[Transmission electron microscopy|TEM]] [[micrograph]] of ''M. tuberculosis''
| taxon = Mycobacterium
| authority = Lehmann & Neumann 1896<ref>{{cite book | vauthors = Lehmann KB, Neumann R | title = Atlas und Grundriss der Bakteriologie und Lehrbuch der speziellen bakteriologischen Diagnostik | trans-title =Atlas and Outline of Bacteriology and Textbook of Special Bacteriological Diagnostics | edition = 1st | publisher = J.F. Lehmann | location = München | year = 1896}}</ref>
| subdivision_ranks = Species
| subdivision = Over 190 species, see [https://lpsn.dsmz.de/genus/mycobacterium LPSN]
| synonyms =
* ''Mycolicibacterium'' <small>Gupta et al. 2018</small>
* ''[[Mycolicibacillus]]'' <small>Gupta et al. 2018</small>
* ''Mycolicibacter'' <small>Gupta et al. 2018</small>
* ''Mycobacteroides'' <small>Gupta et al. 2018</small>
| synonyms_ref = <ref name="LPSN">{{cite web |vauthors=Euzéby JP, Parte AC |url=https://lpsn.dsmz.de/genus/mycobacterium |archive-url=https://web.archive.org/web/20200707151904/https://lpsn.dsmz.de/genus/mycobacterium |url-status=dead |archive-date=July 7, 2020 |title=''Mycobacterium'' |access-date=June 16, 2021 |publisher=[[List of Prokaryotic names with Standing in Nomenclature]] (LPSN) }}</ref>
}}

'''''Mycobacterium''''' is a [[genus]] of over 190 species in the phylum [[Actinomycetota]], assigned its own family, [[Mycobacteriaceae]]. This genus includes [[pathogen]]s known to cause serious diseases in mammals, including [[tuberculosis]] (''[[Mycobacterium tuberculosis|M. tuberculosis]]'') and [[leprosy]] (''[[Mycobacterium leprae|M. leprae]]'') in humans. The [[Greek language|Greek]] prefix ''myco-'' means 'fungus', alluding to this genus' [[Mold (fungus)|mold]]-like colony surfaces.<ref name="Mycobacteria_1999">{{Cite report |url=https://www.epa.gov/sites/default/files/2015-10/documents/mycobacteria-report.pdf |title=Mycobacteria: Health Advisory | work = Environmental Protection Agency |date=August 1999}}</ref> Since this genus has [[cell wall]]s with a waxy lipid-rich outer layer containing high concentrations of mycolic acid,<ref name="pmid32470138">{{cite journal |vauthors=Batt SM, Minnikin DE, Besra GS |title=The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system |journal=The Biochemical Journal |volume=477 |issue=10 |pages=1983–2006 |date=May 2020 |pmid=32470138 |pmc=7261415 |doi=10.1042/BCJ20200194 |url=}}</ref> [[acid-fast staining]] is used to emphasize their resistance to acids, compared to other cell types.<ref name="Pennington_2021">{{cite journal | vauthors = Pennington KM, Vu A, Challener D, Rivera CG, Shweta FN, Zeuli JD, Temesgen Z | title = Approach to the diagnosis and treatment of non-tuberculous mycobacterial disease | journal = Journal of Clinical Tuberculosis and Other Mycobacterial Diseases | volume = 24 | pages = 100244 | date = August 2021 | pmid = 34036184 | pmc = 8135042 | doi = 10.1016/j.jctube.2021.100244 }}</ref>

Mycobacterial species are generally aerobic, non-motile, and capable of growing with minimal nutrition. The genus is divided based on each species' pigment production and growth rate.<ref name="Forbes_2018">{{cite journal | vauthors = Forbes BA, Hall GS, Miller MB, Novak SM, Rowlinson MC, Salfinger M, Somoskövi A, Warshauer DM, Wilson ML | display-authors = 6 | title = Practical Guidance for Clinical Microbiology Laboratories: Mycobacteria | journal = Clinical Microbiology Reviews | volume = 31 | issue = 2 | pages = e00038–17 | date = April 2018 | pmid = 29386234 | pmc = 5967691 | doi = 10.1128/CMR.00038-17 }}</ref> While most ''Mycobacterium'' species are non-pathogenic, the genus' characteristic complex cell wall contributes to evasion from host defenses.<ref name="Dulberger_2020" />

==Microbiology==

=== Morphology ===
[[File:Model of the Mycobacterial Cell Envelope.png|thumb|upright=1.5|Model of the ''Mycobacterium spp.'' cell envelope with 3-D protein structures]]

Mycobacteria are [[aerobic organism|aerobic]] with 0.2-0.6&nbsp;μm wide and 1.0-10&nbsp;μm long [[Bacillus (shape)|rod shapes]]. They are generally [[Non-motile bacteria|non-motile]], except for the species ''[[Mycobacterium marinum]]'', which has been shown to be motile within [[macrophage]]s.<ref>{{cite journal | vauthors = Stamm LM, Morisaki JH, Gao LY, Jeng RL, McDonald KL, Roth R, Takeshita S, Heuser J, Welch MD, Brown EJ | display-authors = 6 | title = Mycobacterium marinum escapes from phagosomes and is propelled by actin-based motility | journal = The Journal of Experimental Medicine | volume = 198 | issue = 9 | pages = 1361–1368 | date = November 2003 | pmid = 14597736 | pmc = 2194249 | doi = 10.1084/jem.20031072 }}</ref> Mycobacteria possess [[Bacterial capsule|capsules]] and most do not form [[endospores]]. ''M. marinum'' and perhaps ''M. bovis'' have been shown to [[spore|sporulate]];<ref>{{cite journal | vauthors = Ghosh J, Larsson P, Singh B, Pettersson BM, Islam NM, Sarkar SN, Dasgupta S, Kirsebom LA | display-authors = 6 | title = Sporulation in mycobacteria | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 26 | pages = 10781–10786 | date = June 2009 | pmid = 19541637 | pmc = 2705590 | doi = 10.1073/pnas.0904104106 | doi-access = free | bibcode = 2009PNAS..10610781G }}</ref> however, this has been contested by further research.<ref>{{cite journal | vauthors = Traag BA, Driks A, Stragier P, Bitter W, Broussard G, Hatfull G, Chu F, Adams KN, Ramakrishnan L, Losick R | display-authors = 6 | title = Do mycobacteria produce endospores? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 2 | pages = 878–881 | date = January 2010 | pmid = 20080769 | pmc = 2818926 | doi = 10.1073/pnas.0911299107 | doi-access = free | bibcode = 2010PNAS..107..878T }}</ref> The distinguishing characteristic of all ''Mycobacterium'' species is a thick, [[hydrophobic]], and [[mycolic acid]]-rich cell wall made of [[peptidoglycan]] and [[arabinogalactan]], with these unique components offering targets for new tuberculosis drugs.<ref name= BhamidiS>{{cite book | vauthors = Bhamidi S|year=2009|chapter=Mycobacterial Cell Wall Arabinogalactan|title=Bacterial Polysaccharides: Current Innovations and Future Trends|publisher=Caister Academic Press|isbn= 978-1-904455-45-5}}</ref>

=== Physiology ===
Many ''Mycobacterium'' species readily grow with minimal nutrients, using [[ammonia]] and/or [[amino acid]]s as nitrogen sources and [[glycerol]] as a carbon source in the presence of mineral salts. Temperatures for optimal growth vary between species and media conditions, ranging from 25 to 45&nbsp;°C.<ref name="Forbes_2018"/>

Most ''Mycobacterium'' species, including most clinically relevant species, can be cultured in [[blood agar]].<ref>{{cite journal | vauthors = Lagier JC, Edouard S, Pagnier I, Mediannikov O, Drancourt M, Raoult D | title = Current and past strategies for bacterial culture in clinical microbiology | journal = Clinical Microbiology Reviews | volume = 28 | issue = 1 | pages = 208–236 | date = January 2015 | pmid = 25567228 | pmc = 4284306 | doi = 10.1128/CMR.00110-14 }}</ref> However, some species grow very slowly due to extremely long reproductive cycles, such as ''[[M. leprae]]'' requiring 12 days per division cycle compared to 20 minutes for some ''E. coli'' strains.<ref>{{cite journal | vauthors = Shepard CC, Mcrae DH | title = Mycobacterium leprae in Mice: Minimal Infectious Dose, Relationship Between Staining Quality and Infectivity, and Effect of Cortisone | journal = Journal of Bacteriology | volume = 89 | issue = 2 | pages = 365–372 | date = February 1965 | pmid = 14255702 | pmc = 305516 | doi = 10.1128/jb.89.2.365-372.1965 }}</ref>

=== Ecology ===
Whereas ''Mycobacterium tuberculosis'' and ''M. leprae'' are pathogenic, most mycobacteria do not cause disease unless they enter skin lesions of those with pulmonary and/or immune dysfunction, despite being widespread across aquatic and terrestrial environments. Through [[biofilm]] formation, cell wall resistance to [[chlorine]], and association with [[amoeba]]s, mycobacteria can survive a variety of environmental stressors. The agar media used for most [[water testing]] does not support the growth of mycobacteria, allowing it to go undetected in municipal and hospital systems.<ref>{{cite journal | vauthors = Vaerewijck MJ, Huys G, Palomino JC, Swings J, Portaels F | title = Mycobacteria in drinking water distribution systems: ecology and significance for human health | journal = FEMS Microbiology Reviews | volume = 29 | issue = 5 | pages = 911–934 | date = November 2005 | pmid = 16219512 | doi = 10.1016/j.femsre.2005.02.001 | doi-access = free }}</ref>

=== Genomics ===
Hundreds of ''Mycobacterium'' genomes have been completely sequenced.<ref>{{Cite web |title=JGI GOLD {{!}} Projects |url=https://gold.jgi.doe.gov/projects?Project.Is+Public=Yes&Organism.Organism+Name=Mycobacterium&Organism.Organism+Name=Mycobacterium&Project.Project+Status=Complete+and+Published&Project.Is+Public=Yes&Project.Project+Status=Complete+and+Published |access-date=2023-05-13 |website=gold.jgi.doe.gov}}</ref>

The genome sizes of mycobacteria range from relatively small ones (e.g. in ''M. leprae'') to quite large ones, such as that as ''[[Mycobacterium vulneris|M. vulneris]],'' encoding 6,653 proteins, larger than the ~6000 proteins of [[Eukaryote|eukaryotic]] [[Saccharomyces cerevisiae|yeast]].<ref>{{cite journal |vauthors=Croce O, Robert C, Raoult D, Drancourt M |date=May 2014 |title=Draft Genome Sequence of Mycobacterium vulneris DSM 45247T |journal=Genome Announcements |volume=2 |issue=3 |doi=10.1128/genomeA.00370-14 |pmc=4014686 |pmid=24812218}}</ref>
{| class="wikitable"
|+Protein-Coding Genomic Information
!Organism
!Number of Protein Coding Genes
|-
|''M. intracellulare''
|5,289<ref>{{Cite web |title=UniProt |url=https://www.uniprot.org/proteomes/UP000595205 |access-date=2023-05-07 |website=www.uniprot.org}}</ref>
|-
|[[Mycobacterium colombiense|''M. colombiense'']]
|5,084<ref>{{Cite web |title=UniProt |url=https://www.uniprot.org/proteomes/UP000250915 |access-date=2023-05-07 |website=www.uniprot.org}}</ref>
|-
|''M. leprae''
|1,603<ref name="uniprot_UP000000806">{{Cite web |title=UniProt |url=https://www.uniprot.org/proteomes/UP000000806 |access-date=2023-05-07 |website=www.uniprot.org}}</ref>
|-
|''M. tuberculosis''
|3,995<ref name="uniprot_UP000000806"/>
|-
|''M. smegmatis''
|6,602<ref>{{Cite web |title=UniProt |url=https://www.uniprot.org/proteomes/UP000000757 |access-date=2023-05-07 |website=www.uniprot.org}}</ref>
|-
|''M. chelonae''
|4,948<ref>{{Cite web |title=UniProt |url=https://www.uniprot.org/proteomes/UP000317728 |access-date=2023-05-07 |website=www.uniprot.org}}</ref>
|}

== Pathogenicity ==

=== ''Mycobacterium tuberculosis'' complex ===
''[[Mycobacterium tuberculosis]]'' can remain latent in human hosts for decades after an initial infection, allowing it to continue infecting others. It has been estimated that a third of the world population has latent tuberculosis (TB).<ref>{{cite journal | vauthors = Getahun H, Matteelli A, Chaisson RE, Raviglione M | title = Latent Mycobacterium tuberculosis infection | journal = The New England Journal of Medicine | volume = 372 | issue = 22 | pages = 2127–2135 | date = May 2015 | pmid = 26017823 | doi = 10.1056/NEJMra1405427 }}</ref> ''M. tuberculosis'' has many [[virulence factor]]s, which can be divided across lipid and fatty acid metabolism, cell envelope proteins, [[macrophage]] inhibitors, [[kinase]] proteins, [[protease]]s, metal-transporter proteins, and gene expression regulators.<ref>{{cite journal | vauthors = Forrellad MA, Klepp LI, Gioffré A, Sabio y García J, Morbidoni HR, de la Paz Santangelo M, Cataldi AA, Bigi F | display-authors = 6 | title = Virulence factors of the Mycobacterium tuberculosis complex | journal = Virulence | volume = 4 | issue = 1 | pages = 3–66 | date = January 2013 | pmid = 23076359 | pmc = 3544749 | doi = 10.4161/viru.22329 }}</ref> Several lineages such as [[Mycobacterium bovis|''M. t.'' var. ''bovis'']] (bovine TB) were considered separate species in the [[Mycobacterium tuberculosis complex|''M, tuberculosis'' complex]] until they were finally merged into the main species in 2018.<ref>{{cite journal |last1=Riojas |first1=Marco A. |last2=McGough |first2=Katya J. |last3=Rider-Riojas |first3=Cristin J. |last4=Rastogi |first4=Nalin |last5=Hazbón |first5=Manzour Hernando |title=Phylogenomic analysis of the species of the Mycobacterium tuberculosis complex demonstrates that Mycobacterium africanum, Mycobacterium bovis, Mycobacterium caprae, Mycobacterium microti and Mycobacterium pinnipedii are later heterotypic synonyms of Mycobacterium tuberculosis |journal=International Journal of Systematic and Evolutionary Microbiology |date=1 January 2018 |volume=68 |issue=1 |pages=324–332 |doi=10.1099/ijsem.0.002507|pmid=29205127 |doi-access=free }}</ref>

=== Leprosy ===
The development of [[leprosy]] is caused by infection with either ''[[Mycobacterium leprae]]'' or ''[[Mycobacterium lepromatosis]]'', two closely related bacteria. Roughly 200,000 new cases of infection are reported each year, and 80% of new cases are reported in Brazil, India, and Indonesia.<ref>{{cite journal | vauthors = Sugawara-Mikami M, Tanigawa K, Kawashima A, Kiriya M, Nakamura Y, Fujiwara Y, Suzuki K | title = Pathogenicity and virulence of ''Mycobacterium leprae'' | journal = Virulence | volume = 13 | issue = 1 | pages = 1985–2011 | date = December 2022 | pmid = 36326715 | pmc = 9635560 | doi = 10.1080/21505594.2022.2141987 }}</ref> ''M. leprae'' infection localizes within the skin macrophages and Schwann cells found in peripheral nerve tissue.

=== Nontuberculosis ''Mycobacteria'' ===
[[File:Three Pathogenic Mycobacteria.png|thumb|[[Sequence homology|Orthologous]] proteins found in each species (based on [[Orthologous MAtrix|OMA]] identifiers). Unique proteins for each species are localized in the outer section for each species.]]
Nontuberculosis ''Mycobacteria'' (NTM), which exclude ''[[Mycobacterium tuberculosis|M. tuberculosis]], [[Mycobacterium leprae|M. leprae]],'' and ''M. lepromatosis,'' can infect mammalian hosts. These bacteria are referred to as "atypical mycobacteria." Although person-to-person transmission is rare, transmission of ''M. abscessus'' has been observed between patients with [[cystic fibrosis]].<ref>{{Cite web |date=2019-08-12 |title=Nontuberculous Mycobacteria (NTM) Infections {{!}} HAI {{!}} CDC |url=https://www.cdc.gov/hai/organisms/nontuberculous-mycobacteria.html |access-date=2023-04-28 |website=www.cdc.gov |language=en-us}}</ref> The four primary diseases observed in humans are chronic pulmonary disease, disseminated disease in immunocompromised patients, skin and soft tissue infections, and superficial lymphadenitis. 80-90% of recorded NTM infections manifest as pulmonary diseases.<ref name="To_2020">{{cite journal | vauthors = To K, Cao R, Yegiazaryan A, Owens J, Venketaraman V | title = General Overview of Nontuberculous Mycobacteria Opportunistic Pathogens: ''Mycobacterium avium'' and ''Mycobacterium abscessus'' | journal = Journal of Clinical Medicine | volume = 9 | issue = 8 | pages = 2541 | date = August 2020 | pmid = 32781595 | pmc = 7463534 | doi = 10.3390/jcm9082541 | doi-access = free }}</ref>

''[[Mycobacteroides abscessus|M. abscessus]]'' is the most virulent rapidly-growing mycobacterium (RGM), as well as the leading cause of RGM based pulmonary infections. Although it has been traditionally viewed as an opportunistic pathogen like other NTMs, analysis of various virulence factors (VFs) have shifted this view to that of a true pathogen. This is due to the presence of known mycobacterial VFs and other non-mycobacterial VFs found in other prokaryotic pathogens.<ref name="To_2020" />

=== Virulence factors ===
Mycobacteria have cell walls with [[peptidoglycan]], [[arabinogalactan]], and [[mycolic acid]]; a waxy outer mycomembrane of mycolic acid; and an outermost [[Bacterial capsule|capsule]] of [[glucan]]s and secreted proteins for virulence. It constantly remodels these layers to survive in stressful environments and avoid host immune defenses. This cell wall structure results in colony surfaces resembling fungi, leading to the genus' use of the Greek prefix ''myco-''.<ref>{{cite web |title=Mycobacteria: Health Advisory EPA-822-B-01-007 |url=https://www.epa.gov/sites/default/files/2015-10/documents/mycobacteria-report.pdf |website=epa.gov |publisher=US Environmental Protection Agency (EPA) |access-date=10 March 2023 |page=2 |date=August 1999}}</ref> This unique structure makes [[penicillin]]s ineffective, instead requiring a multi-drug antibiotic treatment of [[isoniazid]] to inhibit mycolic acid synthesis, [[rifampicin]] to interfere with transcription, [[ethambutol]] to hinder arabinogalactan synthesis, and [[pyrazinamide]] to impede [[coenzyme A]] synthesis.<ref name="Dulberger_2020">{{cite journal | vauthors = Dulberger CL, Rubin EJ, Boutte CC | title = The mycobacterial cell envelope - a moving target | journal = Nature Reviews. Microbiology | volume = 18 | issue = 1 | pages = 47–59 | date = January 2020 | pmid = 31728063 | doi = 10.1038/s41579-019-0273-7 | s2cid = 208020338 }}</ref>
{| class="wikitable"
|+''Mycobacterial'' Infection Information
!Organism
!Common Symptoms of Infection
!Known Treatments
!'''Reported Cases (Region, Year)'''
|-
|''M. tuberculosis''
|Fatigue, weight loss, fever, hemoptysis, chest pain.<ref>{{Cite web |date=2022-08-17 |title=Fact Sheets {{!}} General {{!}} Tuberculosis: General Information {{!}} TB {{!}} CDC |url=https://www.cdc.gov/tb/publications/factsheets/general/tb.htm |access-date=2023-04-25 |website=www.cdc.gov |language=en-us}}</ref>
|isoniazid INH, rifampin, pyrazinamide, ethambutol.<ref>{{Cite web| work = American Lung Association|title=Diagnosing and Treating Tuberculosis |url=https://www.lung.org/lung-health-diseases/lung-disease-lookup/tuberculosis/treating-and-managing |access-date=2023-04-25 |language=en}}</ref>
|1.6 Million (Global, 2021)<ref>{{Cite web |title=Global Tuberculosis Report 2022 |url=https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022 |access-date=2023-05-07 |website=www.who.int |language=en}}</ref>
|-
|''M. leprae''
''M. lepromatosis''
|Skin discoloration, nodule development, dry skin, loss of eyebrows and/or eyelashes, numbness, nosebleeds, paralysis, blindness, nerve pain.<ref name="www.cdc.gov_2018">{{Cite web |date=2018-10-22 |title=Signs and Symptoms {{!}} Hansen's Disease (Leprosy) {{!}} CDC |url=https://www.cdc.gov/leprosy/symptoms/index.html |access-date=2023-04-25 |website=www.cdc.gov |language=en-us}}</ref>
|dapson, rifampicin, clofazimine.<ref name="www.cdc.gov_2018" />
|133,802 (Global, 2021)<ref>{{Cite web |title=Global leprosy (Hansen disease) update, 2021: moving towards interruption of transmission |url=https://www.who.int/publications-detail-redirect/who-wer9736-429-450 |access-date=2023-05-07 |website=www.who.int |language=en}}</ref>
|-
|''M. avium'' complex
|Tender skin, development of boils or pus-filled vesicles, fevers, chills, muscle aches.<ref>{{Cite web |date=2021-11-15 |title=Mycobacterium abscessus in Healthcare Settings {{!}} HAI {{!}} CDC |url=https://www.cdc.gov/hai/organisms/mycobacterium.html |access-date=2023-04-27 |website=www.cdc.gov |language=en-us}}</ref>
|clarithromycin, azithromycin, amikacin, cefoxitin, imipenem.<ref>{{cite journal | vauthors = Weng YW, Huang CK, Sy CL, Wu KS, Tsai HC, Lee SS | title = Treatment for Mycobacterium abscessus complex-lung disease | journal = Journal of the Formosan Medical Association = Taiwan Yi Zhi | volume = 119 | pages = S58–S66 | date = June 2020 | pmid = 32527504 | doi = 10.1016/j.jfma.2020.05.028 | series = Consensus Statement of Nontuberculous Mycobacterial Lung Disease in Taiwan | issue = Suppl 1 | s2cid = 219604813 | doi-access = free }}</ref>
|3000 (US, Annual ''estimated'')<ref>{{Citation | vauthors = Scholar E | title=Mycobacterium Avium-Intracellulare Infections |date=2007-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780080552323608918 |work=xPharm: The Comprehensive Pharmacology Reference |pages=1–5 | veditors = Enna SJ, Bylund DB |access-date=2023-05-07 |place=New York |publisher=Elsevier |language=en |doi=10.1016/b978-008055232-3.60891-8 |isbn=978-0-08-055232-3 |url-access=subscription }}</ref>
|-
|''M. abscessus'' complex
|Coughing, hemoptysis, fever, cavitary lesions.<ref name="Huang_2010">{{cite journal | vauthors = Huang YC, Liu MF, Shen GH, Lin CF, Kao CC, Liu PY, Shi ZY | title = Clinical outcome of Mycobacterium abscessus infection and antimicrobial susceptibility testing | journal = Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi | volume = 43 | issue = 5 | pages = 401–406 | date = October 2010 | pmid = 21075707 | doi = 10.1016/S1684-1182(10)60063-1 }}</ref>
|clarithromycin, amikacin, cefoxitin, imipenem.<ref name="Huang_2010" />
|Unknown
|}

== History ==
{{cladogram|title=Cladogram of Key Species
|caption=
|clades={{clade| style=font-size:75%;line-height:75%;
    |1={{clade
        |label1='''''Mycobacterium'''''
        |1={{clade
            |1={{clade
                |1=''[[Mycobacteroides chelonae|M. chelonae]]''
                |2={{clade
                    |1=''[[Mycobacterium fortuitum|M. fortuitum]]''
                    |2={{clade
                        |1=''[[Mycobacterium flavescens|M. flavescens]]''
                        |2=''[[Mycobacterium smegmatis|M. smegmatis]]''
                        }}
                    }}
                }}
        |2={{clade
            |1={{clade
                |1={{clade
                    |1={{clade
                        |1={{clade
                            |1={{clade
                                |1={{clade
                                    |1={{clade
                                        |1=''[[Mycobacterium avium complex|M. avium]]''
                                        |2=''[[Mycobacterium avium complex|M. intracellulare]]''
                                        }}
                                    |2={{clade
                                        |1=''[[Mycobacterium kansasii|M. kansasii]]''
                                        |2=''[[Mycobacterium scrofulaceum|M. scrofulaceum]]''
                                        }}
                                    }}
                                |2={{clade
                                    |1=''[[Mycobacterium malmoense|M. malmoense]]''
                                    |2=''[[Mycobacterium szulgai|M. szulgai]]''
                                    }}
                                }}
                            |2={{clade
                                |1=''[[Mycobacterium marinum|M. marinum]]''
                                |2=''[[Mycobacterium tuberculosis|M. tuberculosis]]''
                                }}
                            }}
                        |2=''[[Mycobacterium gordonae|M. gordonae]]''
                        }}
                    |2=''[[Mycobacterium simiae|M. simiae]]''
                    }}
                |2=''[[Mycobacterium xenopi|M. xenopi]]''
                }}
            |2={{clade
                |1=''[[Mycolicibacter nonchromogenicus|M. nonchromogenicum]]''
                |2=''[[Mycolicibacter terrae|M. terrae]]''
                }}
            }}
        }}
    |label2=[[Outgroup (cladistics)|outgroup]]
    |2=''[[Nocardia asteroides]]''
    }}
}}}}

Mycobacteria have historically been categorized through [[Phenotypic testing of mycobacteria|phenotypic testing]], such as the [[Runyon classification]] of analyzing growth rate and production of yellow/orange [[carotenoid]] pigments. Group I contains '''[[Slowly growing Mycobacteria#Photochromogenic|photochromogens]]''' (pigment production induced by light), Group II comprises '''[[Slowly growing Mycobacteria#Scotochromogens|scotochromogens]]''' (constitutive pigment production), and the '''[[Slowly growing Mycobacteria#Nonchromogenic|non-chromogens]]''' of Groups III and IV have a pale yellow/tan pigment, regardless of light exposure. Group IV species are "rapidly-growing" mycobacteria compared to the "slowly-growing" Group III species because samples grow into visible colonies in less than seven days.<ref name="Forbes_2018" />

Because the [[International Code of Nomenclature of Prokaryotes|International Code of Nomenclature of Prokaryotes (ICNP)]] currently recognizes 195 ''Mycobacterium'' species, classification and identification systems now rely on [[DNA sequencing]] and [[computational phylogenetics]]. The major disease-causing groups are the [[Mycobacterium tuberculosis complex|''M. tuberculosis'' complex]] ([[tuberculosis]]), [[Mycobacterium avium complex|''M. avium'' complex]] ([[mycobacterium avium-intracellulare infection]]), ''[[Mycobacterium leprae|M. leprae]]'' and ''[[Mycobacterium lepromatosis|M. lepromatosis]]'' ([[leprosy]]), and [[Mycobacteroides abscessus|''M. abscessus'']] ([[Lower respiratory tract infection|chronic lung infection]]).<ref name="Mycobacteria_1999" />

Microbiologist Enrico Tortoli has constructed a phylogenetic tree of the genus' key species based on the earlier genetic sequencing of Rogall, et al. (1990), alongside new phylogentic trees based on Tortoli's 2017 sequencing of 148 ''Mycobacterium'' species:<ref>{{cite book | vauthors = Tortoli E | chapter = Chapter 1 - The Taxonomy of the Genus Mycobacterium |date=2019-01-10 | doi = 10.1016/B978-0-12-814692-7.00001-2 |title = Nontuberculous Mycobacteria (NTM) |pages=1–10 | veditors = Velayati AA, Farnia P |publisher=Academic Press |language=en |isbn=978-0-12-814692-7 | s2cid = 92810288 }}</ref>

<gallery mode=packed heights=360>
File:Phylogentic Tree of Slowly-Growing Mycobacterium Tortoli 2017.png|Phylogenetic tree of slowly-growing members of the Mycobacterium genus
File:Phylogentic Tree of Rapidly-Growing Mycobacterium Tortoli 2017.png|Phylogenetic tree of rapidly-growing members of the ''Mycobacterium'' genus, alongside the M. terrae complex.<ref>{{cite journal | vauthors = Tortoli E, Fedrizzi T, Meehan CJ, Trovato A, Grottola A, Giacobazzi E, Serpini GF, Tagliazucchi S, Fabio A, Bettua C, Bertorelli R, Frascaro F, De Sanctis V, Pecorari M, Jousson O, Segata N, Cirillo DM | display-authors = 6 | title = The new phylogeny of the genus Mycobacterium: The old and the news | journal = Infection, Genetics and Evolution | volume = 56 | pages = 19–25 | date = December 2017 | pmid = 29030295 | doi = 10.1016/j.meegid.2017.10.013 | bibcode = 2017InfGE..56...19T }}</ref>
</gallery>

===Proposed division of the genus===
Gupta ''et al.'' have proposed dividing ''Mycobacterium'' into five genera, based on an analysis of 150 species in this genus. Due to controversy over complicating clinical diagnoses and treatment, all of the renamed species have retained their original identity in the ''Mycobacterium'' genus as a valid taxonomic synonym:<ref name=Gupta2018>{{cite journal | vauthors = Gupta RS, Lo B, Son J | title = Phylogenomics and Comparative Genomic Studies Robustly Support Division of the Genus ''Mycobacterium'' into an Emended Genus ''Mycobacterium'' and Four Novel Genera | journal = Frontiers in Microbiology | volume = 9 | pages = 67 | year = 2018 | pmid = 29497402 | pmc = 5819568 | doi = 10.3389/fmicb.2018.00067 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tortoli E, Brown-Elliott BA, Chalmers JD, Cirillo DM, Daley CL, Emler S, Floto RA, Garcia MJ, Hoefsloot W, Koh WJ, Lange C, Loebinger M, Maurer FP, Morimoto K, Niemann S, Richter E, Turenne CY, Vasireddy R, Vasireddy S, Wagner D, Wallace RJ, Wengenack N, van Ingen J | display-authors = 6 | title = Same meat, different gravy: ignore the new names of mycobacteria | journal = The European Respiratory Journal | volume = 54 | issue = 1 | pages = 1900795 | date = July 2019 | pmid = 31296783 | doi = 10.1183/13993003.00795-2019 | doi-access = free }}</ref>
* '''''Mycobacterium''''' based on the Slowly-Growing Tuberculosis-Simiae clade
* ''[[Mycobacteroides]]'' based on the Rapidly-Growing Abscessus-Chelonae clade
* ''[[Mycolicibacillus]]'' based on the Slowly-Growing Triviale clade
* ''[[Mycolicibacter]]'' based on the Slowly-Growing Terrae clade
* ''[[Mycolicibacterium]]'' based on the Rapidly-Growing Fortuitum-Vaccae clade

{{further|Bacterial taxonomy#Pathology vs. phylogeny}}

==Diagnosis==
The two most common methods for visualizing these acid-fast bacilli as bright red against a blue background are the [[Ziehl–Neelsen stain|Ziehl-Neelsen stain]] and [[Kinyoun stain|modified Kinyoun stain]]. Fite's stain is used to color ''M. leprae'' cells as pink against a blue background. Rapid Modified Auramine O Fluorescent staining has specific binding to slowly-growing mycobacteria for yellow staining against a dark background. Newer methods include Gomori-Methenamine Silver staining and [[Periodic acid–Schiff stain|Perioidic Acid Schiff staining]] to color ''Mycobacterium avium complex'' (MAC) cells black and pink, respectively.<ref name="Pennington_2021" />

While some mycobacteria can take up to eight weeks to grow visible colonies from a cultured sample, most clinically relevant species will grow within the first four weeks, allowing physicians to consider alternative causes if negative readings continue past the first month.<ref>{{cite journal | vauthors = Ogwang S, Mubiri P, Bark CM, Joloba ML, Boom WH, Johnson JL | title = Incubation time of Mycobacterium tuberculosis complex sputum cultures in BACTEC MGIT 960: 4weeks of negative culture is enough for physicians to consider alternative diagnoses | journal = Diagnostic Microbiology and Infectious Disease | volume = 83 | issue = 2 | pages = 162–164 | date = October 2015 | pmid = 26239846 | pmc = 4573350 | doi = 10.1016/j.diagmicrobio.2015.07.002 }}</ref> Growth media include [[Löwenstein–Jensen medium]] and [[mycobacteria growth indicator tube]] (MGIT).
<gallery mode=packed heights=170>
File:Mycobacterium tuberculosis Ziehl-Neelsen stain 02.jpg|''Mycobacterium tuberculosis'' on [[Ziehl–Neelsen stain|Ziehl-Neelsen stain]]
File:Slant tubes of Löwenstein-Jensen medium with control, M tuberculosis, M avium and M gordonae.jpg|Slant tubes of Löwenstein-Jensen medium.<ref group=note>From left to right in image of slant tubes of Löwenstein-Jensen medium:<br />- Negative control<br />- ''[[M. tuberculosis]]'': Dry-appearing colonies<br />- ''[[Mycobacterium avium complex]]'': Wet-appearing colonies<br />- ''[[M. gordonae]]'': Yellowish colonies</ref>
File:Mycobacteria Growth Indicator Tube (MGIT) samples in ultraviolet light.jpg|[[Mycobacteria growth indicator tube|MGIT]] samples emitting fluorescence in ultraviolet light 
</gallery>

== Mycobacteriophages ==
Mycobacteria can be infected by [[mycobacteriophage]]s, a class of viruses with high specificity for their targets. By hijacking the cellular machinery of mycobacteria to produce additional phages, such viruses can be used in [[phage therapy]] for eukaryotic hosts, as they would die alongside the mycobacteria. Since only some mycobacteriophages are capable of penetrating the ''M. tuberculosis'' membrane, the viral DNA may be delivered through artificial [[liposome]]s because bacteria uptake, transcribe, and translate foreign DNA into proteins.<ref>{{cite journal | vauthors = Azimi T, Mosadegh M, Nasiri MJ, Sabour S, Karimaei S, Nasser A | title = Phage therapy as a renewed therapeutic approach to mycobacterial infections: a comprehensive review | language = English | journal = Infection and Drug Resistance | volume = 12 | pages = 2943–2959 | date = 2019-09-17 | pmid = 31571947 | pmc = 6756577 | doi = 10.2147/IDR.S218638 | doi-access = free }}</ref>

== Mycosides ==
Mycosides are [[glycolipid]]s isolated from ''Mycobacterium'' species with Mycoside A found in photochromogenic strains, Mycoside B in bovine strains, and Mycoside C in avian strains.<ref>{{cite journal | vauthors = Smith DW, Randall HM, Maclennan AP, Lederer E | title = Mycosides: a new class of type-specific glycolipids of Mycobacteria | journal = Nature | volume = 186 | issue = 4728 | pages = 887–888 | date = June 1960 | pmid = 13831939 | doi = 10.1038/186887a0 | s2cid = 4149360 | bibcode = 1960Natur.186..887S }}</ref> Different forms of Mycoside C have varying success as a receptor to inactivate [[mycobacteriophage]]s.<ref>{{cite journal | vauthors = Goren MB, McClatchy JK, Martens B, Brokl O | title = Mycosides C: behavior as receptor site substance for mycobacteriophage D4 | journal = Journal of Virology | volume = 9 | issue = 6 | pages = 999–1003 | date = June 1972 | pmid = 4113889 | pmc = 356406 | doi = 10.1128/jvi.9.6.999-1003.1972 }}</ref> Replacement of the gene encoding [[mycocerosic acid synthase]] in ''M. bovis'' prevents formation of mycosides.<ref>{{cite journal | vauthors = Azad AK, Sirakova TD, Rogers LM, Kolattukudy PE | title = Targeted replacement of the mycocerosic acid synthase gene in Mycobacterium bovis BCG produces a mutant that lacks mycosides | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 10 | pages = 4787–4792 | date = May 1996 | pmid = 8643481 | pmc = 39357 | doi = 10.1073/pnas.93.10.4787 | doi-access = free | bibcode = 1996PNAS...93.4787A }}</ref>

==Notes==
<references group="note"/>

== References ==
{{Reflist|2}}

== External links ==
* [https://www.bv-brc.org/view/Taxonomy/1763 Bacterial and Viral Bioinformatics Resource Center]: Genomes, proteins, epitopes, and pathways of mycobacteria
* [https://www.merckmanuals.com/professional/infectious-diseases/mycobacteria Merck Manual - Mycobacteria]
* [https://mycobrowser.epfl.ch/ Mycobrowser]: Genomic and proteomic database for pathogenic mycobacteria
* [https://www.cdc.gov/hai/organisms/nontuberculous-mycobacteria.html CDC - Nontuberculous Mycobacteria (NTM) Infections]
* [http://app.chuv.ch/prasite/index.html PRASITE: Identification of Mycobacteria]
* [https://web.archive.org/web/20170302163233/http://www.webtb.org/ TB Structural Genomics Consortium]

{{Mycobacteria}}
{{Taxonbar|from=Q194309}}
{{Authority control}}

[[Category:Acid-fast bacilli]]
[[Category:Tuberculosis]]
[[Category:Bacterial diseases]]
[[Category:Bacteria genera]]
[[Category:Mycobacteria| ]]
[[Category:Pathogenic bacteria]]
[[Category:Infectious causes of cancer]]