The study by Gagneux et al. investigates the global population structure of *Mycobacterium tuberculosis* and its implications for transmission dynamics and control. The authors identified six main phylogeographical lineages of *M. tuberculosis*, each associated with specific human populations. In an urban setting like San Francisco, mycobacterial lineages were more likely to spread among sympatric (cohabiting) patient populations compared to allopatric (separately living) populations. The findings suggest that particular mycobacterial lineages are adapted to specific human populations, with higher transmission rates observed in sympatric cases. This adaptation is particularly evident in high-risk individuals with impaired host resistance. The study has important implications for tuberculosis control and vaccine development, highlighting the need to consider strain genetic variation and host-specific adaptations when designing new vaccines.The study by Gagneux et al. investigates the global population structure of *Mycobacterium tuberculosis* and its implications for transmission dynamics and control. The authors identified six main phylogeographical lineages of *M. tuberculosis*, each associated with specific human populations. In an urban setting like San Francisco, mycobacterial lineages were more likely to spread among sympatric (cohabiting) patient populations compared to allopatric (separately living) populations. The findings suggest that particular mycobacterial lineages are adapted to specific human populations, with higher transmission rates observed in sympatric cases. This adaptation is particularly evident in high-risk individuals with impaired host resistance. The study has important implications for tuberculosis control and vaccine development, highlighting the need to consider strain genetic variation and host-specific adaptations when designing new vaccines.