Tuberculosis caused 20% of all human deaths in the Western world between the 17th and 19th centuries, and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. Here we used 259 whole-genome sequences to reconstruct the evolutionary history of the Mycobacterium tuberculosis complex (MTBC). Coalescent analyses indicate that MTBC emerged about 70 thousand years ago, accompanied migrations of anatomically modern humans out of Africa, and expanded as a consequence of increases in human population density during the Neolithic. This long co-evolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low- and high host densities.

Molecular typing of 964 specimens from patients in Ethiopia with lymph node or pulmonary tuberculosis showed a similar distribution of Mycobacterium tuberculosis strains between the 2 disease manifestations and a minimal role for M. bovis. We report a novel phylogenetic lineage of M. tuberculosis strongly associated with the Horn of Africa.

Several human pathogens are to be found within the bacterial genus Mycobacterium, notably Mycobacterium tuberculosis, the causative agent of tuberculosis, one of the most threatening of human infectious diseases, with an annual lethality of about two million people. The characteristic mycobacterial cell envelope is the dominant feature of the biology of M. tuberculosis and other mycobacterial pathogens, based on sugars and lipids of exceptional structure. The cell wall consists of a peptidoglycan-arabinogalactan-mycolic acid complex beyond the plasma membrane. Free-standing lipids, lipoglycans, and proteins intercalate within this complex, complement the mycolic acid monolayer and may also appear in a capsular-like arrangement. The consequences of these structural oddities are an extremely robust and impermeable cell envelope. This review reflects on these entities from the perspective of their synthesis, particularly the structural and functional aspects of the glycosyltransferases (GTs) of M. tuberculosis, the dominating group of enzymes responsible for the terminal stages of their biosynthesis. Besides the many nucleotide-sugar dependent GTs with orthologs in prokaryotes and eukaryotes, M. tuberculosis and related species of the order Actinomycetales, in light of the highly lipophilic environment prevailing within the cell envelope, carry a significant number of GTs of the GT-C class dependent on polyprenyl-phosphate-linked sugars. These are of special emphasis in this review.

BackgroundBovine tuberculosis (bTB), caused by Mycobacterium bovis, is a debilitating disease of cattle. Ethiopia has one of the largest cattle populations in the world, with an economy highly dependent on its livestock. Furthermore, Ethiopia has one of the highest incidence rates of human extrapulmonary TB in the world, a clinical presentation that is often associated with transmission of M. bovis from cattle to humans.Methodology/Principal FindingsHere we present a comprehensive investigation of the prevalence of bTB in Ethiopia based on cases identified at slaughterhouses. Out of approximately 32,800 inspected cattle, ∼4.7% showed suspect tuberculous lesions. Culture of suspect lesions yielded acid-fast bacilli in ∼11% of cases, with M. bovis accounting for 58 of 171 acid-fast cultures, while 53 isolates were non-tuberculous mycobacteria. Strikingly, M. tuberculosis was isolated from eight cattle, an unusual finding that suggests human to animal transmission.Conclusions/SignificanceOur analysis has revealed that bTB is widely spread throughout Ethiopia, albeit at a low prevalence, and provides underpinning evidence for public health policy formulation.

We have identified a clonal complex of Mycobacterium bovis present at high frequency in cattle in population samples from several sub-Saharan west-central African countries. This closely related group of bacteria is defined by a specific chromosomal deletion (RDAf1) and can be identified by the absence of spacer 30 in the standard spoligotype typing scheme. We have named this group of strains the African 1 (Af1) clonal complex and have defined the spoligotype signature of this clonal complex as being the same as the M. bovis BCG vaccine strain but with the deletion of spacer 30. Strains of the Af1 clonal complex were found at high frequency in population samples of M. bovis from cattle in Mali, Cameroon, Nigeria, and Chad, and using a combination of variable-number tandem repeat typing and spoligotyping, we show that the population of M. bovis in each of these countries is distinct, suggesting that the recent mixing of strains between countries is not common in this area of Africa. Strains with the Af1-specific deletion (RDAf1) were not identified in M. bovis isolates from Algeria, Burundi, Ethiopia, Madagascar, Mozambique, South Africa, Tanzania, and Uganda. Furthermore, the spoligotype signature of the Af1 clonal complex has not been identified in population samples of bovine tuberculosis from Europe, Iran, and South America. These observations suggest that the Af1 clonal complex is geographically localized, albeit to several African countries, and we suggest that the dominance of the clonal complex in this region is the result of an original introduction into cows naïve to bovine tuberculosis.