| Mycobacterium | |
|---|---|
 | |
| TEMmicrograph ofM. tuberculosis | |
Scientific classification | |
| Domain: | Bacteria |
| Kingdom: | Bacillati |
| Phylum: | Actinomycetota |
| Class: | Actinomycetia |
| Order: | Mycobacteriales |
| Family: | Mycobacteriaceae |
| Genus: | Mycobacterium Lehmann & Neumann 1896[1] |
| Species | |
Over 190 species, seeLPSN | |
| Synonyms[2] | |
| |
Mycobacterium is agenus of over 190 species in the phylumActinomycetota, assigned its own family,Mycobacteriaceae. This genus includespathogens known to cause serious diseases in mammals, includingtuberculosis (M. tuberculosis) andleprosy (M. leprae) in humans. TheGreek prefixmyco- means 'fungus', alluding to this genus'mold-like colony surfaces.[3] Since this genus hascell walls with a waxy lipid-rich outer layer containing high concentrations of mycolic acid,[4]acid-fast staining is used to emphasize their resistance to acids, compared to other cell types.[5]
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.[6] While mostMycobacterium species are non-pathogenic, the genus' characteristic complex cell wall contributes to evasion from host defenses.[7]
Mycobacteria areaerobic with 0.2-0.6 μm wide and 1.0-10 μm longrod shapes. They are generallynon-motile, except for the speciesMycobacterium marinum, which has been shown to be motile withinmacrophages.[8] Mycobacteria possesscapsules and most do not formendospores.M. marinum and perhapsM. bovis have been shown tosporulate;[9] however, this has been contested by further research.[10] The distinguishing characteristic of allMycobacterium species is a thick,hydrophobic, andmycolic acid-rich cell wall made ofpeptidoglycan andarabinogalactan, with these unique components offering targets for new tuberculosis drugs.[11]
ManyMycobacterium species readily grow with minimal nutrients, usingammonia and/oramino acids as nitrogen sources andglycerol 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 °C.[6]
MostMycobacterium species, including most clinically relevant species, can be cultured inblood agar.[12] However, some species grow very slowly due to extremely long reproductive cycles, such asM. leprae requiring 12 days per division cycle compared to 20 minutes for someE. coli strains.[13]
WhereasMycobacterium tuberculosis andM. 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. Throughbiofilm formation, cell wall resistance tochlorine, and association withamoebas, mycobacteria can survive a variety of environmental stressors. The agar media used for mostwater testing does not support the growth of mycobacteria, allowing it to go undetected in municipal and hospital systems.[14]
Hundreds ofMycobacterium genomes have been completely sequenced.[15]
The genome sizes of mycobacteria range from relatively small ones (e.g. inM. leprae) to quite large ones, such as that asM. vulneris, encoding 6,653 proteins, larger than the ~6000 proteins ofeukaryoticyeast.[16]
| Organism | Number of Protein Coding Genes |
|---|---|
| M. intracellulare | 5,289[17] |
| M. colombiense | 5,084[18] |
| M. leprae | 1,603[19] |
| M. tuberculosis | 3,995[19] |
| M. smegmatis | 6,602[20] |
| M. chelonae | 4,948[21] |
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).[22]M. tuberculosis has manyvirulence factors, which can be divided across lipid and fatty acid metabolism, cell envelope proteins,macrophage inhibitors,kinase proteins,proteases, metal-transporter proteins, and gene expression regulators.[23] Several lineages such asM. t. var.bovis (bovine TB) were considered separate species in theM, tuberculosis complex until they were finally merged into the main species in 2018.[24]
The development ofleprosy is caused by infection with eitherMycobacterium leprae orMycobacterium 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.[25]M. leprae infection localizes within the skin macrophages and Schwann cells found in peripheral nerve tissue.
NontuberculosisMycobacteria (NTM), which excludeM. tuberculosis,M. leprae, andM. lepromatosis, can infect mammalian hosts. These bacteria are referred to as "atypical mycobacteria." Although person-to-person transmission is rare, transmission ofM. abscessus has been observed between patients withcystic fibrosis.[26] 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.[27]
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.[27]
Mycobacteria have cell walls withpeptidoglycan,arabinogalactan, andmycolic acid; a waxy outer mycomembrane of mycolic acid; and an outermostcapsule ofglucans 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 prefixmyco-.[28] This unique structure makespenicillins ineffective, instead requiring a multi-drug antibiotic treatment ofisoniazid to inhibit mycolic acid synthesis,rifampicin to interfere with transcription,ethambutol to hinder arabinogalactan synthesis, andpyrazinamide to impedecoenzyme A synthesis.[7]
| Organism | Common Symptoms of Infection | Known Treatments | Reported Cases (Region, Year) |
|---|---|---|---|
| M. tuberculosis | Fatigue, weight loss, fever, hemoptysis, chest pain.[29] | isoniazid INH, rifampin, pyrazinamide, ethambutol.[30] | 1.6 Million (Global, 2021)[31] |
| M. leprae M. lepromatosis | Skin discoloration, nodule development, dry skin, loss of eyebrows and/or eyelashes, numbness, nosebleeds, paralysis, blindness, nerve pain.[32] | dapson, rifampicin, clofazimine.[32] | 133,802 (Global, 2021)[33] |
| M. avium complex | Tender skin, development of boils or pus-filled vesicles, fevers, chills, muscle aches.[34] | clarithromycin, azithromycin, amikacin, cefoxitin, imipenem.[35] | 3000 (US, Annualestimated)[36] |
| M. abscessus complex | Coughing, hemoptysis, fever, cavitary lesions.[37] | clarithromycin, amikacin, cefoxitin, imipenem.[37] | Unknown |
| Cladogram of Key Species |
Mycobacteria have historically been categorized throughphenotypic testing, such as theRunyon classification of analyzing growth rate and production of yellow/orangecarotenoid pigments. Group I containsphotochromogens (pigment production induced by light), Group II comprisesscotochromogens (constitutive pigment production), and thenon-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.[6]
Because theInternational Code of Nomenclature of Prokaryotes (ICNP) currently recognizes 195Mycobacterium species, classification and identification systems now rely onDNA sequencing andcomputational phylogenetics. The major disease-causing groups are theM. tuberculosis complex (tuberculosis),M. avium complex (mycobacterium avium-intracellulare infection),M. leprae andM. lepromatosis (leprosy), andM. abscessus (chronic lung infection).[3]
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 148Mycobacterium species:[38]
![Phylogenetic tree of rapidly-growing members of the Mycobacterium genus, alongside the M. terrae complex.[39]](/mt/?noimg=&dark=on&url=https%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aPhylogentic_Tree_of_Rapidly-Growing_Mycobacterium_Tortoli_2017.png)
Guptaet al. have proposed dividingMycobacterium 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 theMycobacterium genus as a valid taxonomic synonym:[40][41]
The two most common methods for visualizing these acid-fast bacilli as bright red against a blue background are theZiehl-Neelsen stain andmodified Kinyoun stain. Fite's stain is used to colorM. 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 andPerioidic Acid Schiff staining to colorMycobacterium avium complex (MAC) cells black and pink, respectively.[5]
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.[42] Growth media includeLöwenstein–Jensen medium andmycobacteria growth indicator tube (MGIT).
![Slant tubes of Löwenstein-Jensen medium.[note 1]](/mt/?noimg=&dark=on&url=https%3a%2f%2fen.wikipedia.org%2fwiki%2fFile%3aSlant_tubes_of_L%25C3%25B6wenstein-Jensen_medium_with_control%2c_M_tuberculosis%2c_M_avium_and_M_gordonae.jpg)
_samples_in_ultraviolet_light.jpg)
Mycobacteria can be infected bymycobacteriophages, 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 inphage therapy for eukaryotic hosts, as they would die alongside the mycobacteria. Since only some mycobacteriophages are capable of penetrating theM. tuberculosis membrane, the viral DNA may be delivered through artificialliposomes because bacteria uptake, transcribe, and translate foreign DNA into proteins.[43]
Mycosides areglycolipids isolated fromMycobacterium species with Mycoside A found in photochromogenic strains, Mycoside B in bovine strains, and Mycoside C in avian strains.[44] Different forms of Mycoside C have varying success as a receptor to inactivatemycobacteriophages.[45] Replacement of the gene encoding mycocerosic acid synthase inM. bovis prevents formation of mycosides.[46]
