Abstract
Tuberculosis (TB) is a disease of antiquity. Yet TB today still causes more adult deaths than any other single infectious disease. Recent studies show that contrary to the common view postulating an animal origin for TB, Mycobacterium tuberculosis complex (MTBC), the causative agent of TB, emerged as a human pathogen in Africa and colonized the world accompanying the Out-of-Africa migrations of modern humans. More recently, evolutionarily ‘modern’ lineages of MTBC expanded as a consequence of the global human population increase, and spread throughout the world following waves of exploration, trade and conquest. While epidemiological data suggest that the different phylogenetic lineages of MTBC might have adapted to different human populations, overall, the phylogenetically ‘modern’ MTBC lineages are more successful in terms of their geographical spread compared with the ‘ancient’ lineages. Interestingly, the global success of ‘modern’ MTBC correlates with a hypo-inflammatory phenotype in macrophages, possibly reflecting higher virulence, and a shorter latency in humans. Finally, various human genetic variants have been associated with different MTBC lineages, suggesting an interaction between human genetic diversity and MTBC variation. In summary, the biology and the epidemiology of human TB have been shaped by the long-standing association between MTBC and its human host.
Highlights
Tuberculosis (TB) remains a major global health problem
FROM MYCOBACTERIUM TUBERCULOSIS COMPLEX GENOTYPE TO PHENOTYPE The first human cells encountered by Mycobacterium tuberculosis complex (MTBC) during the course of an initial infection are believed to be alveolar macrophages [24]
The results showed that the monocyte-derived macrophages (MDMs) infected with different MTBC strains differed markedly in the levels of cytokines and chemokines produced
Summary
Tuberculosis (TB) remains a major global health problem. Ten million new TB cases and 2 million deaths are estimated to occur each year, more than any time in history [1]. M. canettii shows clear evidence of ongoing horizontal gene exchange (figure 1), which does not occur in classical MTBC [21,22] This latter observation, combined with the lack of evidence for human-to-human transmission of M. canettii, and the fact that M. cannettii clinical isolates are rare, suggests that this organism is an opportunist, and that an environmental reservoir exists somewhere in the Horn of Africa [23]. M. tuberculosis and M. africanum are obligate human pathogens with limited survival outside of the human body and no known animal reservoir [15] These microbes have to cause active disease in order to transmit to secondary hosts [24]. Extrapulmonary TB is generally non-infectious and has a lower public health priority [1]
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Schedule a callMore From: Philosophical Transactions of the Royal Society B: Biological Sciences
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