Mycobacterium

Microbiologic characteristics

Mycobacteria are aerobic and nonmotile bacteria (except for the species Mycobacterium marinum, which has been shown to be motile within macrophages) that are characteristically acid fast. Mycobacteria have an outer membrane. They do not have capsules, and most do not form endospores. Mycobacterium marinum and perhaps M. bovis have been shown to sporulate; however, this has been contested by further research. 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.

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. 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. In addition, the availability of genetic manipulation techniques still lags far behind that of other bacterial species.

A natural division occurs between slowly– and rapidly–growing species. Mycobacteria that form colonies clearly visible to the naked eye within seven days on subculture are termed rapid growers, while those requiring longer periods are termed slow growers. Mycobacteria cells are straight or slightly curved rods between 0.2 and 0.6 µm wide and between 1.0 and 10 µm long.

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. xenopi, M. szulgai.

Non-chromogens (Groups III & 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

Ex: M. fortuitum, M. chelonae

Staining characteristics

Mycobacteria are classical acid-fast organisms. 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.

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, surface and secreted proteins of M. tuberculosis contribute significantly to the virulence of this organism. There is an increasing list of extracytoplasmic proteins proven to have a function in the virulence of M. tuberculosis.

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. There are 18 and 20 carbon atoms in mycosides A, and B, respectively.

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, suggesting that these two genera are closely related.

Species

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.

Mycobacterium tuberculosis complex

Also see main article about Mycobacterium tuberculosis complex.

Mycobacterium tuberculosis complex (MTBC) members are causative agents of human and animal tuberculosis. Species in this complex include:M. africanumM. bovisM. bovis BCGM. canettiM. capraeM. microtiM. mungiM. orygisM. pinnipediiM. suricattaeM. tuberculosis, the major cause of human tuberculosis

Mycobacterium avium complex

Mycobacterium avium complex (MAC) is a group of species that, in a disseminated infection but not lung infection, used to be a significant cause of death in AIDS patients. The species M. indicus pranii appears to be basal in this complex. Species in this complex include:M. aviumM. avium paratuberculosis, which has been implicated in Crohn's disease in humans and is the causative agent of Johne's disease in cattle and sheepM. avium silvaticumM. avium "hominissuis"M. colombienseM. indicus pranii M.intacellulare

Mycobacterium gordonae clade

M. asiaticum

M. gordonae

Mycobacterium kansasii clade

M. gastri

M. kansasii

Mycobacterium nonchromogenicum/terrae clade

M. hiberniae

M. nonchromogenicum

M. terrae

M. triviale

Mycolactone-producing mycobacteria

M. ulcerans, which causes the "Buruli", or "Bairnsdale" ulcer

M. pseudoshottsii

M. shottsii

Mycobacterium simiae clade

M. triplex

M. genavense

M. florentinum

M. lentiflavum

M. palustre

M. kubicae

M. parascrofulaceum

M. heidelbergense

M. interjectum

M. simiae

Ungrouped

M. bohemicum

M. botniense

M. branderi

M. celatum

M. chimaera

M. conspicuum

M. cookii

M. doricum

M. farcinogenes

M. haemophilum

M. heckeshornense

M. intracellulare

M. lacus

M. leprae, which causes leprosy

M. lepraemurium

M. lepromatosis, another (less significant) cause of leprosy, described in 2008

M. liflandii

M. malmoense

M. marinum, causes a rare disease called Aquarium granuloma.

M. monacense

M. montefiorense

M. murale

M. nebraskense

M. saskatchewanense

M. scrofulaceum

M. shimoidei

M. szulgai

M. tusciae

M. xenopi

M. yongonense

Intermediate growth rate

M. intermedium

Mycobacterium chelonae clade

M. abscessus

M. bolletii

M. chelonae

Mycobacterium fortuitum clade

M. boenickei

M. brisbanense

M. cosmeticum

M. fortuitum

M. fortuitum subsp. acetamidolyticum

M. houstonense

M. mageritense

M. neworleansense

M. peregrinum

M. porcinum

M. senegalense

M. septicum

Mycobacterium mucogenicum clade

Mycobacterium aubagnese

M. mucogenicum

Mycobacterium phocaicum

Mycobacterium parafortuitum clade

M. austroafricanum

M. diernhoferi

M. frederiksbergense

M. hodleri

M. neoaurum

M. parafortuitum

Mycobacterium vaccae clade

M. aurum

M. vaccae

CF

M. chitae

M. fallax

Ungrouped

M. agri

M. aichiense

M. alvei

M. arupense

M. barrassiae

M. brumae

M. canariasense

M. chubuense

M. conceptionense

M. confluentis

M. duvalii

M. elephantis

M. flavescens

M. gadium

M. gilvum

M. hassiacum

M. holsaticum

M. immunogenum

M. komossense

M. madagascariense

M. massiliense

M. massilipolynesiensis

M. moriokaense

M. obuense

M. phlei

M. psychrotolerans

M. pulveris

M. pyrenivorans

M. smegmatis

M. goodii

M. wolinskyi

M. sphagni

M. thermoresistibile

M. vanbaalenii

Ungrouped

M. arosiense

M. aubagnense

M. chlorophenolicum

M. fluoroanthenivorans

M. kumamotonense

M. novocastrense

M. parmense

M. poriferae

M. rhodesiae

M. seoulense

M. tokaiense

Mycobacteriophage

Mycobacteria can be infected by Mycobacteriophage, bacterial viruses that may be used in the future to treat tuberculosis and related diseases by phage therapy.