出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/04/23 10:50:04」(JST)
| Mycobacterium tuberculosis | |
|---|---|
| M. tuberculosis bacterial colonies | |
| Scientific classification | |
| Kingdom: | Bacteria |
| Phylum: | Actinobacteria |
| Class: | Actinobacteria |
| Order: | Actinomycetales |
| Suborder: | Corynebacterineae |
| Family: | Mycobacteriaceae |
| Genus: | Mycobacterium |
| Species: | M. tuberculosis |
| Binomial name | |
| Mycobacterium tuberculosis Zopf 1883 |
|
| Synonyms | |
|
Tubercle bacillus Koch 1882 |
|
Mycobacterium tuberculosis (MTB) is a pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of most cases of tuberculosis (TB).[1] First discovered in 1882 by Robert Koch, M. tuberculosis has an unusual, waxy coating on its cell surface (primarily mycolic acid), which makes the cells impervious to Gram staining. Acid-fast detection techniques are used instead. The physiology of M. tuberculosis is highly aerobic and requires high levels of oxygen. Primarily a pathogen of the mammalian respiratory system, MTB infects the lungs. The most frequently used diagnostic methods for TB are the tuberculin skin test, acid-fast stain, and chest radiographs.[1]
The M. tuberculosis genome was sequenced in 1998.[2][3]
M. tuberculosis requires oxygen to grow. It does not retain any bacteriological stain due to high lipid content in its wall, hence Ziehl-Neelsen staining, or acid-fast staining, is used. Despite this, it is considered a Gram-positive bacteria. While mycobacteria do not seem to fit the Gram-positive category from an empirical standpoint (i.e., they do not retain the crystal violet stain), they are classified as acid-fast Gram-positive bacteria due to their lack of an outer cell membrane.[1]
M. tuberculosis divides every 15–20 hours, which is extremely slow compared to other bacteria, which tend to have division times measured in minutes (Escherichia coli can divide roughly every 20 minutes). It is a small bacillus that can withstand weak disinfectants and can survive in a dry state for weeks. Its unusual cell wall, rich in lipids (e.g., mycolic acid), is likely responsible for this resistance and is a key virulence factor.[4]
When in the lungs, M. tuberculosis is taken up by alveolar macrophages, but they are unable to digest the bacterium. Its cell wall prevents the fusion of the phagosome with a lysosome. Specifically, M. tuberculosis blocks the bridging molecule, early endosomal autoantigen 1 (EEA1); however, this blockade does not prevent fusion of vesicles filled with nutrients. Consequently, the bacteria multiply unchecked within the macrophage. The bacteria also carry the UreC gene, which prevents acidification of the phagosome.[5] In addition, production of the diterpene Isotuberculosinol prevents maturation of the phagosome.[6] The bacteria also evade macrophage-killing by neutralizing reactive nitrogen intermediates.[7]
The ability to construct M. tuberculosis mutants and test individual gene products for specific functions has significantly advanced our understanding of the pathogenesis and virulence factors of M. tuberculosis. Many secreted and exported proteins are known to be important in pathogenesis.[8]
M. tuberculosis comes from the genus Mycobacterium, which is composed of approximately 100 recognized and proposed species. The most familiar of the species are M. tuberculosis and M. leprae (leprosy).[9]
M. tuberculosis is genetically diverse, which results in significant phenotypic differences between clinical isolates. Different strains of M. tuberculosis are associated with different geographic regions. However, phenotypic studies suggest that strain variation never has implications for the development of new diagnostics and vaccines. Microevolutionary variation does affect the relative fitness and transmission dynamics of antibiotic-resistant strains.[10]
Typing of strains is useful in the investigation of tuberculosis outbreaks, because it gives the investigator evidence for-or-against transmission from person to person. Consider the situation where person A has tuberculosis and believes that he acquired it from person B. If the bacteria isolated from each person belong to different types, then transmission from B to A is definitively disproved; on the other hand, if the bacteria are the same strain, then this supports (but does not definitively prove) the theory that B infected A.
Until the early 2000s, M. tuberculosis strains were typed by pulsed field gel electrophoresis (PFGE).[11][12] This has now been superseded by variable numbers of tandem repeats (VNTR), which is technically easier to perform and allows better discrimination between strains. This method makes use of the presence of repeated DNA sequences within the M. tuberculosis genome.
There are three generations of VNTR typing for M. tuberculosis. The first scheme, called ETR (exact tandem repeat), used only five loci,[13] but the resolution afforded by these five loci was not as good as PFGE. The second scheme, called MIRU (mycobacterial interspersed repetitive unit) had discrimination as good as PFGE.[14][15] The third generation (MIRU2) added a further nine loci to bring the total to 24. This provides a degree of resolution greater than PFGE and is currently the standard for typing M. tuberculosis.[16]
Mycobacterium outbreaks are often caused by hypervirulent strains of M. tuberculosis. In laboratory experiments, these clinical isolates elicit unusual immunopathology, and may be either hyperinflammatory or hypoinflammatory. Studies have shown the majority of hypervirulent mutants have deletions in their cell wall-modifying enzymes or regulators that respond to environmental stimuli. Studies of these mutants have indicated the mechanisms that enable M. tuberculosis to mask its full pathogenic potential, inducing a granuloma that provides a protective niche, and enable the bacilli to sustain a long-term, persistent infection.[17]
M. tuberculosis is characterized by caseating granulomas containing Langhans giant cells, which have a "horseshoe" pattern of nuclei. Organisms are identified by their red color on acid-fast staining.
The genome of the H37Rv strain was published in 1998.[18] Its size is 4 million base pairs, with 3959 genes; 40% of these genes have had their function characterised, with possible function postulated for another 44%. Within the genome are also six pseudogenes.
The genome contains 250 genes involved in fatty acid metabolism, with 39 of these involved in the polyketide metabolism generating the waxy coat. Such large numbers of conserved genes show the evolutionary importance of the waxy coat to pathogen survival.
About 10% of the coding capacity is taken up by the PE/PPE gene families that encode acidic, glycine-rich proteins. These proteins have a conserved N-terminal motif, deletion of which impairs growth in macrophages and granulomas.[19]
Nine noncoding sRNAs have been characterised in M. tuberculosis,[20] with a further 56 predicted in a bioinformatics screen.[21]
In 2013, a study on the genome of several sensitive, ultra-resistant and multiresistant M. tuberculosis strains was made to study antibiotic resistance mechanisms. Results reveal new relationships and drug resistance genes not previously associated and suggest that some genes and intergenic regions associated with drug resistance may be involved in the resistance to more than one drug. Noteworthy is the role that the intergenic regions in the development of this resistance, and that most of the genes that are proposed in this study to be responsible for drug resistance have an essential role in the development of M. tuberculosis.[22]
The Mycobacterium tuberculosis complex evolved in Africa and most probably in the Horn of Africa.[23] The M. tuberculosis group has a number of members that include Mycobacterium africanum, Mycobacterium bovis (Dassie's bacillus), Mycobacterium caprae, Mycobacterium microti, Mycobacterium mungi, Mycobacterium orygis and Mycobacterium pinnipedii. This group may also include the Mycobacterium canettii clade.
The M. canettii clade — which includes Mycobacterium prototuberculosis — are a group of smooth colony Mycobacterium species. Unlike the established members of the M. tuberculosis group they undergo recombination with other species. The majority of the known strains of this group have been isolated from the Horn of Africa. The ancestor of Mycobacterium tuberculosis appears to be the species Mycobacterium canettii.[24] M canettii itself was first described in 1969.
The established members of the M. tuberculosis complex are all clonal in their spread. The main human infecting species have been classified into seven spoligotypes: type 1 contains the East African-Indian (EAI) and some Manu (Indian) strains; type 2 is the Beijing group; type 3 consists of the Central Asian (CAS) strains; type 4 of the Ghana and Haarlem (H/T), Latin America-Mediterranean (LAM) and X strains; types 5 and 6 correspond to Mycobacterium africanum and are observed predominantly and at very high frequency in West Africa. A seventh type has been isolated from the Horn of Africa.[23] The other species of this complex belong to a number of spoligotypes and do not normally infect humans.
Type 2 and 3 are more closely related to each other than to the other types. Types 5 and 6 are most closely aligned with the species that do not normally infect humans. Type 3 has been divided into two clades: CAS-Kili (found in Tanzania) and CAS-Delhi (found in India and Saudi Arabia).
The most recent common ancestor of the M. tuberculosis complex evolved ~40,000 years ago.[25] The most recent common ancestor of the EAI and LAM strains has been estimated to be 13,700 and 7,000 years ago respectively. The Beijing- CAS strains diverged ~17,100 years ago. All types of the M. tuberculosis began their current expansion ~5000 years ago—a period that coincides with the appearance of Mycobacterium bovis. The Beijing strain appears to have been the most successful with a ~500 increase in effective population size (Ne) since its expansion began. The least successful of the main linages appears to be have been those limited to Africa where they have undergone an Ne increase of only 5 fold. Since its initial evolution M. bovis has undergone an expansion of its Ne of ~65 fold.
M. tuberculosis, then known as the "tubercle bacillus", was first described on 24 March 1882 by Robert Koch, who subsequently received the Nobel Prize in physiology or medicine for this discovery in 1905; the bacterium is also known as "Koch's bacillus".[26]
Tuberculosis has existed throughout history, but the name has changed frequently over time. In 1720, though, the history of tuberculosis started to take shape into what is known of it today; as the physician Benjamin Marten described in his A Theory of Consumption, tuberculosis may be caused by small living creatures that are transmitted through the air to other patients.[27]
The BCG vaccine has been developed with success in preventing tuberculosis.
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| リンク元 | 「tubercle bacilli」「tubercle bacillus」 |
| 関連記事 | 「Md」「M」 |