Mycobacterium

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Mycobacterium
Mycobacterium tuberculosis 01.jpg
TEM micrograph of M. tuberculosis.
Scientific classification
Domain:
Phylum:
Order:
Suborder:
Family:
Mycobacteriaceae
Genus:
Mycobacterium

Lehmann & Neumann 1896
Species

See below.

Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. Over 190 species are recognized in this genus. [1] This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ( Mycobacterium tuberculosis ) and leprosy ( Mycobacterium leprae ) in humans. [2] The Greek prefix myco- means "fungus," alluding to the way mycobacteria have been observed to grow in a mold-like fashion on the surface of cultures. [3] It is acid fast and cannot be stained by the Gram stain procedure.

Contents

Microbiologic characteristics

Metabolism and morphology

Mycobacterial cell wall: 1-outer lipids, 2-mycolic acid, 3-polysaccharides (arabinogalactan), 4-peptidoglycan, 5-plasma membrane, 6-lipoarabinomannan (LAM), 7-phosphatidylinositol mannoside, 8-cell wall skeleton Mycobacterial cell wall diagram.svg
Mycobacterial cell wall: 1-outer lipids, 2-mycolic acid, 3-polysaccharides (arabinogalactan), 4-peptidoglycan, 5-plasma membrane, 6-lipoarabinomannan (LAM), 7-phosphatidylinositol mannoside, 8-cell wall skeleton

Mycobacteria are aerobic. They are bacillary in form, at least in most phases that have attracted human microbiological attention to date; they are straight or slightly curved rods between 0.2 and 0.6 µm wide and between 1.0 and 10 µm long. They are generally nonmotile bacteria, except for the species Mycobacterium marinum , which has been shown to be motile within macrophages. They are characteristically acid-fast. [2] Mycobacteria have an outer membrane. [4] They possess capsules, and most do not form endospores. M. marinum and perhaps M. bovis have been shown to sporulate; [5] however, this has been contested by further research. [6] The distinguishing characteristic of all Mycobacterium species is that the cell wall is thicker than in many other bacteria, being hydrophobic, waxy, and rich in mycolic acids/mycolates. The cell wall consists of the hydrophobic mycolate layer and a peptidoglycan layer held together by a polysaccharide, arabinogalactan. The cell wall makes a substantial contribution to the hardiness of this genus. The biosynthetic pathways of cell wall components are potential targets for new drugs for tuberculosis. [7]

Many Mycobacterium species adapt readily to growth on very simple substrates, using ammonia or amino acids as nitrogen sources and glycerol as a carbon source in the presence of mineral salts. Optimum growth temperatures vary widely according to the species and range from 25 °C to over 50 °C.

Most Mycobacterium species, including most clinically relevant species, can be cultured in blood agar. [8] However, some species grow very slowly due to extremely long reproductive cycles— M. leprae , may take more than 20 days to proceed through one division cycle (for comparison, some E. coli strains take only 20 minutes), making laboratory culture a slow process. [2] In addition, the availability of genetic manipulation techniques still lags far behind that of other bacterial species. [9]

A natural division occurs between slowly- and rapidly-growing species. Mycobacteria that form colonies clearly visible to the naked eye within 7 days on subculture are termed rapid growers, while those requiring longer periods are termed slow growers.

Pigmentation

Some mycobacteria produce carotenoid pigments without light. Others require photoactivation for pigment production.

Photochromogens (Group I)
Produce nonpigmented colonies when grown in the dark and pigmented colonies only after exposure to light and reincubation.
  • Ex: M. kansasii, M. marinum, M. simiae.
Scotochromogens (Group II)
Produce deep yellow to orange colonies when grown in the presence of either the light or the dark.
  • Ex: M. scrofulaceum, M. gordonae, M. szulgai.
Non-chromogens (Groups III and IV)
Nonpigmented in the light and dark or have only a pale yellow, buff or tan pigment that does not intensify after light exposure.
  • Ex: M. tuberculosis, M. avium-intra-cellulare, M. bovis, M. ulcerans, M. xenopi
  • Ex: M. fortuitum, M. chelonae

Staining characteristics

Mycobacteria are classical acid-fast organisms. [10] Stains used in evaluation of tissue specimens or microbiological specimens include Fite's stain, Ziehl-Neelsen stain, and Kinyoun stain.

Mycobacteria appear phenotypically most closely related to members of Nocardia , Rhodococcus , and Corynebacterium .

Ecology

Mycobacteria are widespread organisms, typically living in water (including tap water treated with chlorine) and food sources. Some, however, including the tuberculosis and the leprosy organisms, appear to be obligate parasites and are not found as free-living members of the genus.

Pathogenicity

Mycobacteria can colonize their hosts without the hosts showing any adverse signs. For example, billions of people around the world have asymptomatic infections of M. tuberculosis (citation needed).

Mycobacterial infections are notoriously difficult to treat. The organisms are hardy due to their cell wall, which is neither truly Gram negative nor positive. In addition, they are naturally resistant to a number of antibiotics that disrupt cell-wall biosynthesis, such as penicillin. Due to their unique cell wall, they can survive long exposure to acids, alkalis, detergents, oxidative bursts, lysis by complement, and many antibiotics. Most mycobacteria are susceptible to the antibiotics clarithromycin and rifamycin, but antibiotic-resistant strains have emerged.

As with other bacterial pathogens, M. tuberculosis produces a number of surface and secreted proteins that contribute to its virulence. However, the mechanism by which these proteins contribute to virulence remains unknown. [11]

Medical classification

Mycobacteria can be classified into several major groups for purpose of diagnosis and treatment: M. tuberculosis complex, which can cause tuberculosis: M. tuberculosis, M. bovis, M. africanum, and M. microti; M. leprae, which causes Hansen's disease or leprosy; nontuberculous mycobacteria (NTM) are all the other mycobacteria, which can cause pulmonary disease resembling tuberculosis, lymphadenitis, skin disease, or disseminated disease.

Mycosides

Mycosides are phenolic alcohols (such as phenolphthiocerol) that were shown to be components of Mycobacterium glycolipids that are termed glycosides of phenolphthiocerol dimycocerosate. [12] Mycosides A and B have 18 and 20 carbon atoms, respectively. [13]

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. [14] [15] Additionally, 14 proteins are found only in the species from the genera Mycobacterium and Nocardia , suggesting that these two genera are closely related. [15]

The genomes of some mycobacteria are quite large when compared to other bacteria. For instance, the genome of M. vulneris encodes 6,653 proteins, which is larger than that of small eukaryotes such as yeast (which encodes only ~6,000 proteins). [16]

Evolution

M. ulcerans evolved from M. marinum. [17]

Species

Phylogenetic position of the tubercle bacilli within the genus Mycobacterium:
The blue triangle corresponds to tubercle bacilli sequences that are identical or differing by a single nucleotide. The sequences of the genus Mycobacterium that matched most closely to those of M. tuberculosis were retrieved from the BIBI database (http://pbil.univ-lyon.fr/bibi/) and aligned with those obtained for 17 smooth and MTBC strains. The unrooted neighbor-joining tree is based on 1,325 aligned nucleotide positions of the 16S rRNA gene. The scale gives the pairwise distances after Jukes-Cantor correction. Bootstrap support values higher than 90% are indicated at the nodes. Mycobacterium phylogenetic tree.svg
Phylogenetic position of the tubercle bacilli within the genus Mycobacterium:
The blue triangle corresponds to tubercle bacilli sequences that are identical or differing by a single nucleotide. The sequences of the genus Mycobacterium that matched most closely to those of M. tuberculosis were retrieved from the BIBI database (http://pbil.univ-lyon.fr/bibi/) and aligned with those obtained for 17 smooth and MTBC strains. The unrooted neighbor-joining tree is based on 1,325 aligned nucleotide positions of the 16S rRNA gene. The scale gives the pairwise distances after Jukes-Cantor correction. Bootstrap support values higher than 90% are indicated at the nodes.

Phenotypic tests can be used to identify and distinguish different mycobacteria species and strains. In older systems, mycobacteria are grouped based upon their appearance and rate of growth. However, these are symplesiomorphies, and more recent classification is based upon cladistics. Over 100 species are currently recognised.

O'Neill and coworkers recently presented a comprehensive phylogenetic analysis based on an alignment of core genomes of 57 strains of bacteria, including all available mycobacteria. [18]

Slowly growing

Runyon's group I, II and III

Mycobacterium tuberculosis complex

Also see main article about Mycobacterium tuberculosis complex

Mycobacterium avium complex

Mycobacterium gordonae clade

Mycobacterium kansasii clade

Mycobacterium nonchromogenicum/terrae clade

Mycolactone-producing mycobacteria

Mycobacterium simiae clade

Ungrouped

Intermediate growth rate

Rapidly growing

Mycobacterium abscessus clade

Together they are known as the M. abscessus complex

Mycobacterium chelonae clade

Mycobacterium fortuitum clade

Mycobacterium mucogenicum clade

Mycobacterium parafortuitum clade

Mycobacterium vaccae clade

CF

Ungrouped

Ungrouped

Proposed division of the genus

Gupta et al. have, based on the analysis of 150 species in the genus, proposed dividing Mycobacterium into five genera. [19] The proposed new genera are:

Wider acceptance of this proposal is awaited.

Mycobacteriophage

Mycobacteria can be infected by mycobacteriophages, bacterial viruses that may be used in the future to treat tuberculosis and related diseases by phage therapy. The procedure may not go into practice in the case of Mtb for some time, as bacteriophage particles cannot penetrate into the tuberculosis bacilli, or clumps.

Related Research Articles

<i>Mycobacterium tuberculosis</i> Species of bacterium

Mycobacterium tuberculosis 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 cell surface primarily due to the presence of mycolic acid. This coating makes the cells impervious to Gram staining, and as a result, M. tuberculosis can appear either Gram-negative or Gram-positive. Acid-fast stains such as Ziehl-Neelsen, or fluorescent stains such as auramine are used instead to identify M. tuberculosis with a microscope. The physiology of M. tuberculosis is highly aerobic and requires high levels of oxygen. Primarily a pathogen of the mammalian respiratory system, it infects the lungs. The most frequently used diagnostic methods for tuberculosis are the tuberculin skin test, acid-fast stain, culture, and polymerase chain reaction.

<i>Mycobacterium leprae</i> species of bacterium; form of Leprosy

Mycobacterium leprae is a bacterium that causes leprosy, also known as "Hansen’s disease", which is a chronic infectious disease that damages the peripheral nerves and targets the skin, eyes, nose, and muscles. Leprosy can occur at all ages from infancy to elderly, but is curable in which treatments can avert disabilities. It was discovered in 1873 by the Norwegian physician Gerhard Armauer Hansen, who was searching for the bacteria in the skin nodules of patients with leprosy. It was the first bacterium to be identified as causing disease in humans.

Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT), are mycobacteria which do not cause tuberculosis or leprosy. NTM do cause pulmonary diseases that resemble tuberculosis. Mycobacteriosis is any of these illnesses, usually meant to exclude tuberculosis. They occur in many animals, including humans.

<i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> subspecies of bacterium

Mycobacterium avium subspecies paratuberculosis (MAP) is an obligate pathogenic bacterium in the genus Mycobacterium. It is often abbreviated M. paratuberculosis or M. avium ssp. paratuberculosis. It is the causative agent of Johne's disease, which affects ruminants such as cattle, and suspected causative agent in human Crohn's disease and rheumatoid arthritis. The type strain is ATCC 19698.

Ziehl–Neelsen stain microbiological method for identification

Ziehl-Neelsen staining is a type of Acid-fast stain, first introduced by Paul Ehrlich. Ziehl–Neelsen staining is a bacteriological stain used to identify acid-fast organisms, mainly Mycobacteria. It is named for two German doctors who modified the stain: the bacteriologist Franz Ziehl (1859–1926) and the pathologist Friedrich Neelsen (1854–1898).

<i>Mycobacterium smegmatis</i> species of bacterium

Mycobacterium smegmatis is an acid-fast bacterial species in the phylum Actinobacteria and the genus Mycobacterium. It is 3.0 to 5.0 µm long with a bacillus shape and can be stained by Ziehl-Neelsen method and the auramine-rhodamine fluorescent method. It was first reported in November 1884 by Lustgarten, who found a bacillus with the staining appearance of tubercle bacilli in syphilitic chancres. Subsequent to this, Alvarez and Tavel found organisms similar to that described by Lustgarten also in normal genital secretions (smegma). This organism was later named M. smegmatis.

Tuberculous lymphadenitis

Tuberculous lymphadenitis is the most common form of tuberculosis infections that appears outside the lungs. Tuberculous lymphadenitis is a chronic, specific granulomatous inflammation of the lymph node with caseation necrosis, caused by infection with Mycobacterium tuberculosis or related bacteria.

<i>Mycobacterium avium-intracellulare</i> infection Human disease

Mycobacterium avium-intracellulare infection (MAI) is an atypical mycobacterial infection, i.e. one with nontuberculous mycobacteria or NTM, caused by Mycobacterium avium complex ("MAC"), which is made of two mycobacteria species, M. avium and M. intracellulare. This infection causes respiratory illness in birds, pigs, and humans, especially in immunocompromised people. In the later stages of AIDS it can be very severe. It usually first presents as a persistent cough. It is typically treated with a series of three antibiotics for a period of at least six months.

<i>Mycobacterium ulcerans</i> species of bacterium

Mycobacterium ulcerans is a slow-growing mycobacterium that classically infects the skin and subcutaneous tissues, giving rise to indolent nonulcerated and ulcerated lesions. After tuberculosis and leprosy, Buruli ulcer is the third most common mycobacteriosis of humans. M. ulcerans grows optimally on routine mycobacteriologic media at 33 °C and elaborates a necrotizing immunosuppressive cytotoxin (mycolactone). The bacteria are considered microaerophilic. Large ulcers almost certainly caused by M. ulcerans were first observed by Cook in Uganda in 1897; however, the etiologic agent was not isolated and characterized until 1948 in Australia by MacCallum and associates.

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 agent of tuberculosis, more than 4,200 mycobacteriophage have since been isolated from various environmental and clinical sources. Almost 1400 have been completely sequenced. Mycobacteriophages have served as examples of viral lysogeny and of the divergent morphology and genetic arrangement characteristic of many phage types.

Mycobacterium ulcerans liflandii has been isolated from Xenopus tropicalis and Xenopus laevis in a laboratory in the US and causes a Mycobacterium ulcerans-like disease in anurans. The strain was unofficially titled under its own species name until it was renamed to be an ecovariation of Mycobacterium ulcerans.

The 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.

Mycobacterium marinum is a free-living bacterium, which causes opportunistic infections in humans. M. marinum sometimes causes a rare disease known as aquarium granuloma, which typically affects individuals who work with fish or keep home aquariums.

Lipoarabinomannan, also called LAM, is a glycolipid, and a virulence factor associated with Mycobacterium tuberculosis, the bacteria responsible for tuberculosis. Its primary function is to inactivate macrophages and scavenge oxidative radicals.

<i>Mycobacterium fortuitum</i> species of bacterium

Mycobacterium fortuitum is a nontuberculous species of the phylum Actinobacteria, belonging to the genus Mycobacterium.

Mycobacterium immunogenum is a species of the phylum Actinobacteria, belonging to the genus Mycobacterium.

Mycobacterium avium complex is a group of mycobacteria comprising Mycobacterium intracellulare and Mycobacterium avium that are commonly grouped together because they infect humans together; this group, in turn, is part of the group of nontuberculous mycobacteria. These bacteria cause disease in humans called Mycobacterium avium-intracellulare infection or Mycobacterium avium complex infection. This group should not be confused with Mycobacterium tuberculosis complex.

Mycobacteria that form colonies clearly visible to the naked eye in more than 7 days on subculture are termed slow growers.

Mycobacterium scrofulaceum is a species of Mycobacterium.

Lalita Ramakrishnan Professor of Medicine and Infectious Disease at the University of Cambridge

Lalita Ramakrishnan is an American microbiologist who is known for her contributions to the understanding of the biological mechanism of tuberculosis. As of 2019 she serves as a Professor of Immunology and Infectious Diseases at the University of Cambridge, where she is also a Wellcome Trust Principal Research Fellow and a practicing physician. Her research is conducted at the Medical Research Council Laboratory of Molecular Biology, where she serves as the Head of the Molecular Immunity Unit of the Department of Medicine embedded at the MRC LMB. Working with Stanley Falkow at Stanford, she developed the strategy of using Mycobacterium marinum infection as a model for tuberculosis. Her work has appeared in a number of journals, including Science, Nature, and Cell. In 2018 and 2019 Ramakrishnan coauthored two influential papers in the British Medical Journal (BMJ) arguing that the widely accepted estimates of the prevalence of latent tuberculosis -- estimates used as a basis for allocation of research funds -- are far too high.

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Further reading