Generalist and specialist species differ in the breadth of their ecological niche. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis Lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that Lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that while the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of Lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.

These results suggest that resistance formation in Giardia to nitazoxanide and metronidazole is correlated with altered expression of genes involved in stress response such as heat-shock proteins.

SUMMARY The Mycobacterium tuberculosis genome is more heterogenous and less genetically stable within the host than previously thought. Currently, only limited data exist on the within-host microevolution, diversity, and genetic stability of M. tuberculosis. As a direct consequence, our ability to infer M. tuberculosis transmission chains and to understand the full complexity of drug resistance profiles in individual patients is limited. Furthermore, apart from the acquisition of certain drug resistance-conferring mutations, our knowledge on the function of genetic variants that emerge within a host and their phenotypic impact remains scarce. We performed a systematic literature review of whole-genome sequencing studies of serial and parallel isolates to summarize the knowledge on genetic diversity and within-host microevolution of M. tuberculosis. We identified genomic loci of within-host emerged variants found across multiple studies and determined their functional relevance. We discuss important remaining knowledge gaps and finally make suggestions on the way forward.