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|Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra)
Species: Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra)
Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex (TaxID: 419947)
||Acid-fast, obligate aerobic, non-motile, rod-shaped bacterium, this is the causative agent of tuberculosis. Tuberculosis is, to this day, according to the WHO, the leading killer of adults, with approximately 2 million deaths annually worldwide. It is estimated that 8 million people are infected each year. A large part of its success as a pathogen is due to its ability to persist in a dormant or latent form for years or even decades, with a concomitant absence of clinical symptoms. This non-replicating persistent form is refractory to most drugs, it may be induced by hypoxia (oxygen depletion) and/or nitric oxide exposure. Up to one-third of the world's population is thought to be latently infected. An additional problem is the emergence of drug resistant strains, mainly because people do not complete their treatment plans or have been incorrectly treated and so have remained infectious.
The highly attenuated H37Ra (and the already sequenced virulent H37Rv) strains of M. tuberculosis were derived by serial passaging of the H37 clinical isolate through laboratory media. The genetic basis for the avirulent phenotype of M. tuberculosis H37Ra in animal models is not known. Since the H37Ra strain does not revert to a virulent phenotype on passaging through animals, it is likely that the former has acquired multiple point mutations or small deletions/rearrangements in genes crucial for virulence. Some differences between the two strain have been noted. Although both H37Rv and H37Ra are able to infect macrophages equally, only H37Rv and not H37Ra was able to grow intracellularly as well as cause significant mitochondrial damage leading to necrosis. The aggregation of mycobacteria into structures known as "cords" has long been associated with virulence. Comparative gene expression analysis recently identified 22 genes that were consistently expressed at higher levels in H37Rv (a cording strain) than in H37Ra (a non-cording strain) under a variety of growth conditions. More than half of these genes were either involved in lipid metabolism or were putative cell membrane proteins (adapted from PubMed 17435310). Comparisons between H37Ra, H37Rv and the clinical strain CDC 1551 identified 76 single nucleotide polymorphisms in 32 genes, among which mutations affecting transcription factors and/or global metabolic regulations related to in vitro survival under aging stress, and mutations affecting cell envelope, primary metabolism, in vivo growth as well as variations in the PE/PPE/PE-PGRS family genes (encoding proteins with functions such as virulence, fibronectin binding, and cell surface antigenic variations) may underlie the basis of virulence attenuation (adapted from PMID 18584054).
Mycobacteria have an unusual outer membrane approximately 8nm thick, despite being considered Gram-positive. The outer membrane and the mycolic acid-arabinoglactan-peptidoglycan polymer form the cell wall, which constitutes an efficient permeability barrier in conjunction with the cell inner membrane.
Presence of flagella:
Animal pathogen in Mammalia; Avirulent strain
Number of membranes:
Strain: ATCC 25177 / H37Ra
Zheng H., Lu L., Wang B., Pu S., Zhang X., Zhu G., Shi W., Zhang L., Wang H., Wang S., Zhao G., Zhang Y. ;
"Genetic basis of virulence attenuation revealed by comparative genomic analysis of Mycobacterium tuberculosis strain H37Ra versus H37Rv.";
PLoS ONE 3:E2375-E2375(2008).