Journal
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
Volume 83, Issue 2, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MMBR.00062-18
Keywords
Mycobacterium tuberculosis; drug resistance; evolution; whole-genome sequencing; within-host
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Funding
- South African Medical Research Council
- Swiss National Science Foundation [P2BSP3_165379]
- Flemish Fund for Scientific Research [FWO G0F8316N]
- Swiss National Science Foundation (SNF) [P2BSP3_165379] Funding Source: Swiss National Science Foundation (SNF)
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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.
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