Multiplexed Strain Phenotyping Defines Consequences of Genetic Diversity in Mycobacterium tuberculosis for Infection and Vaccination Outcomes

Autor: Allison F. Carey, Xin Wang, Nico Cicchetti, Caitlin N. Spaulding, Qingyun Liu, Forrest Hopkins, Jessica Brown, Jaimie Sixsmith, Rujapak Sutiwisesak, Samuel M. Behar, Thomas R. Ioerger, Sarah M. Fortune
Rok vydání: 2022
Předmět:
Zdroj: mSystems. 7(3)
ISSN: 2379-5077
Popis: There is growing evidence that genetic diversity in Mycobacterium tuberculosis, the causative agent of tuberculosis, contributes to the outcomes of infection and public health interventions, such as vaccination. Epidemiological studies suggest that among the phylogeographic lineages of M. tuberculosis, strains belonging to a sublineage of Lineage 2 (mL2) are associated with concerning clinical features, including hypervirulence, treatment failure, and vaccine escape. The global expansion and increasing prevalence of this sublineage has been attributed to the selective advantage conferred by these characteristics, yet confounding host and environmental factors make it difficult to identify the bacterial determinants driving these associations in human studies. Here, we developed a molecular barcoding strategy to facilitate high-throughput, experimental phenotyping of M. tuberculosis clinical isolates. This approach allowed us to characterize growth dynamics for a panel of genetically diverse M. tuberculosis strains during infection and after vaccination in the mouse model. We found that mL2 strains exhibit distinct growth dynamics
Databáze: OpenAIRE