''Mycobacterium'' is a
genus of over 190 species in the phylum
Actinomycetota, assigned its own family,
Mycobacteriaceae
''Mycobacteriaceae'' is a family of bacteria in the phylum Actinomycetota
The ''Actinomycetota'' (or ''Actinobacteria'') are a phylum of all gram-positive bacteria. They can be terrestrial or aquatic. They are of great economic importance t ...
. This genus includes
pathogens known to cause serious diseases in mammals, including
tuberculosis (''
M. tuberculosis
''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...
'') and
leprosy (''
M. leprae
''Mycobacterium leprae'' (also known as the leprosy bacillus or Hansen's bacillus), is one
of the two species of bacteria that cause Hansen’s disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and ...
'') in humans. The
Greek prefix ''myco-'' means 'fungus', alluding to this genus'
mold-like colony surfaces.
Since this genus has
cell walls
A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...
with
Gram-positive and
Gram-negative features,
acid-fast staining is used to emphasize their resistance to acids, compared to other cell types.
Metabolism and Morphology
Mycobacteria are
aerobic with 0.2-0.6 µm wide and 1.0-10 µm long
rod shapes. They are generally
non-motile
Sessility is the biological property of an organism describing its lack of a means of self-locomotion. Sessile organisms for which natural ''motility'' is absent are normally immobile. This is distinct from the botanical concept of sessility, ...
, except for the species ''
Mycobacterium marinum'', which has been shown to be motile within
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s. Mycobacteria possess
capsules and most do not form
endospores. ''M. marinum'' and perhaps ''M. bovis'' have been shown to
sporulate
In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, f ...
; however, this has been contested by further research. 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.
Many ''Mycobacterium'' species readily grow with minimal nutrients, using
ammonia and/or
amino acids 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 25-45°C.
Most ''Mycobacterium'' species, including most clinically relevant species, can be cultured in
blood agar
An agar plate is a Petri dish that contains a growth medium solidified with agar, used to Microbiological culture, culture microorganisms. Sometimes selective compounds are added to influence growth, such as antibiotics.
Individual microorganism ...
. However, some species grow very slowly due to extremely long reproductive cycles, such as ''
M. leprae
''Mycobacterium leprae'' (also known as the leprosy bacillus or Hansen's bacillus), is one
of the two species of bacteria that cause Hansen’s disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and ...
'' requiring 12 days per division cycle compared to 20 minutes for some ''E. coli'' strains.
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
amoebas, mycobacteria can survive a variety of environmental stressors. The agar media used for most
water testing
Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as a ...
does not support the growth of mycobacteria, allowing it to go undetected in municipal and hospital systems.
Pathogenicity
''
Mycobacterium tuberculosis
''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...
'' can remain latent in human hosts, decades after an initial infection, to continue infecting others. It has been estimated that a third of the world population has latent tuberculosis (TB). ''M. tuberculosis'' has many
virulence factors
Virulence factors (preferably known as pathogenicity factors or effectors in plant science) are cellular structures, molecules and regulatory systems that enable microbial pathogens (bacteria, viruses, fungi, and protozoa) to achieve the following ...
, which can be divided across lipid and fatty acid metabolism, cell envelope proteins,
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
inhibitors,
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
proteins,
proteases, metal-transporter proteins, and gene expression regulators.
Mycobacteria have cell walls with
peptidoglycan,
arabinogalactan, and
mycolic acid; a waxy outer mycomembrane of mycolic acid; and an outermost
capsule of
glucans
A glucan is a polysaccharide derived from D-glucose, linked by glycosidic bonds. Glucans are noted in two forms: alpha glucans and beta glucans. Many beta-glucans are medically important. They represent a drug target for antifungal medications of ...
and secreted proteins for virulence. It constantly remodels these layers to survive in stressful environments and avoid host immune defenses. This unique structure makes
penicillins ineffective, instead requiring a multi-drug antibiotic treatment of
isoniazid to inhibit mycolic acid synthesis,
rifampicin
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), mycobacterium avium complex, ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. ...
to interfere with transcription,
ethambutol to hinder arabinogalactan synthesis, and
pyrazinamide to impede Coenzyme A synthesis.
Genomics
Comparative analyses of mycobacterial genomes have identified several conserved
indels and signature proteins that are uniquely found in all sequenced species from the genus ''Mycobacterium''.
Additionally, 14 proteins are found only in the species from the genera ''Mycobacterium'' and ''
Nocardia
''Nocardia'' is a genus of weakly staining Gram-positive, catalase-positive, rod-shaped bacteria. It forms partially acid-fast beaded branching filaments (acting as fungi, but being truly bacteria). It contains a total of 85 species. Some spec ...
'', suggesting that these two genera are closely related.
The genomes of some mycobacteria are quite large, such as ''M. vulneris'' encoding 6,653 proteins, larger than the ~6000 proteins of
eukaryotic yeast.
Species
Mycobacteria have historically been categorized through
phenotypic testing, such as the
Runyon classification
The Timpe and Runyon classification of nontuberculous mycobacteria based on the rate of growth, production of yellow pigment and whether this pigment was produced in the dark or only after exposure to light.
It was introduced by Ernest Runyon in ...
of analyzing growth rate and production of yellow/orange
carotenoid
Carotenoids (), also called tetraterpenoids, are yellow, orange, and red organic compound, organic pigments that are produced by plants and algae, as well as several bacteria, and Fungus, fungi. Carotenoids give the characteristic color to pumpki ...
pigments. Group I contains photochromogens (pigment production induced by light), Group II comprises scotochromogens (constitutive pigment production), and the 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" species because samples grow into visible colonies in less than seven days.
Because the
International Code of Nomenclature of Prokaryotes (ICNP) currently recognizes 195 ''Mycobacterium'' species, classification and identification systems now rely on
DNA sequencing
DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...
and
computational phylogenetics. The major disease-causing groups are the
Mycobacterium tuberculosis complex (
tuberculosis),
Mycobacterium avium complex (
mycobacterium avium-intracellulare infection), ''
M. leprae
''Mycobacterium leprae'' (also known as the leprosy bacillus or Hansen's bacillus), is one
of the two species of bacteria that cause Hansen’s disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and ...
'' and ''
M. lepromatosis'' (
leprosy), and
Mycobacterium abscessus (
chronic lung infection).
Microbiologist Enrico Tortoli has constructed a phylogentic 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:
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:
* ''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
Diagnosis
The two most common methods for visualizing these acid-fast bacilli as bright red against a blue background are the
Ziehl-Neelsen stain and
modified Kinyoun stain. Fite's stain is used to color ''M. leprae'' cells as pink against a blue background. Rapid Modified Auramine O Florescent staining has specific binding to slowly-growing mycobacteria for yellow staining against a dark background. Newer methods include Gomori-Methenamine Silver staining and
Perioidic Acid Schiff staining to color ''Mycobacterium avium complex'' (MAC) cells black and pink, respectively.
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.
Mycobacteriophages
Mycobacteria can be infected by
mycobacteriophages
A mycobacteriophage is a member of a group of bacteriophages known to have mycobacteria as host bacterial species. While originally isolated from the bacterial species ''Mycobacterium smegmatis'' and ''Mycobacterium tuberculosis'', the causative ...
, 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
liposomes
A liposome is a small artificial Vesicle (biology and chemistry), vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, lipo ...
because bacteria uptake, transcribe, and translate foreign DNA into proteins.
Mycosides
Mycosides are
glycolipids isolated from ''Mycobacterium'' species with Mycoside A found in photochromogenic strains, Mycoside B in bovine strains, and Mycoside C in avian strains. Different forms of Mycoside C have varying success as a receptor to inactivate
mycobacteriophages
A mycobacteriophage is a member of a group of bacteriophages known to have mycobacteria as host bacterial species. While originally isolated from the bacterial species ''Mycobacterium smegmatis'' and ''Mycobacterium tuberculosis'', the causative ...
. Replacement of the gene encoding mycocerosic acid synthase in ''M. bovis'' prevents formation of mycosides.
References
External links
Bacterial and Viral Bioinformatics Resource Center Genomes, proteins, epitopes, and pathways of mycobacteria
Merck Manual - MycobacteriaMycobrowser Genomic and proteomic database for pathogenic mycobacteria
TB Structural Genomics Consortium
{{Taxonbar, from=Q194309
Acid-fast bacilli
Tuberculosis
Bacteriology
Bacterial diseases
Bacteria genera
Mycobacteria
Pathogenic bacteria
Infectious causes of cancer