02071nas a2200397 4500000000100000008004100001653003000042653003700072653002200109653001300131653001400144653001100158653002700169653003100196653001800227653001700245100001400262700001500276700001000291700001700301700001200318700001600330700001300346700001400359700001300373700001700386700001200403700001600415700001200431245007200443856008000515300001200595490000800607520104400615022001401659 2006 d10aAdaptation, Physiological10aDisease Transmission, Infectious10aGenetic Variation10aGenomics10aGeography10aHumans10aMolecular Epidemiology10aMycobacterium tuberculosis10aSan Francisco10aTuberculosis1 aGagneux S1 aDeRiemer K1 aVan T1 aKato-Maeda M1 aJong BC1 aNarayanan S1 aNicol MP1 aNiemann S1 aKremer K1 aGutierrez CM1 aHilty M1 aHopewell PC1 aSmall P00aVariable host-pathogen compatibility in Mycobacterium tuberculosis. uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413851/pdf/pnas-0511240103.pdf a2869-730 v1033 a

Mycobacterium tuberculosis remains a major cause of morbidity and mortality worldwide. Studies have reported human pathogens to have geographically structured population genetics, some of which have been linked to ancient human migrations. However, no study has addressed the potential evolutionary consequences of such longstanding human-pathogen associations. Here, we demonstrate that the global population structure of M. tuberculosis is defined by six phylogeographical lineages, each associated with specific, sympatric human populations. In an urban cosmopolitan environment, mycobacterial lineages were much more likely to spread in sympatric than in allopatric patient populations. Tuberculosis cases that did occur in allopatric hosts disproportionately involved high-risk individuals with impaired host resistance. These observations suggest that mycobacterial lineages are adapted to particular human populations. If confirmed, our findings have important implications for tuberculosis control and vaccine development.

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