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Within host evolution selects for a dominant genotype of Mycobacterium tuberculosis while T cells increase pathogen genetic diversity

Copin, Richard and Wang, Xueying and Louie, Eddie and Escuyer, Vincent and Coscolla, Mireia and Gagneux, Sebastien and Palmer, Guy H. and Ernst, Joel D.. (2016) Within host evolution selects for a dominant genotype of Mycobacterium tuberculosis while T cells increase pathogen genetic diversity. PLoS Pathogens, 12 (12). e1006111.

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Abstract

Molecular epidemiological assessments, drug treatment optimization, and development of immunological interventions all depend on understanding pathogen adaptation and genetic variation, which differ for specific pathogens. Mycobacterium tuberculosis is an exceptionally successful human pathogen, yet beyond knowledge that this bacterium has low overall genomic variation but acquires drug resistance mutations, little is known of the factors that drive its population genomic characteristics. Here, we compared the genetic diversity of the bacteria that established infection to the bacterial populations obtained from infected tissues during murine M. tuberculosis pulmonary infection and human disseminated M. bovis BCG infection. We found that new mutations accumulate during in vitro culture, but that in vivo, purifying selection against new mutations dominates, indicating that M. tuberculosis follows a dominant lineage model of evolution. Comparing bacterial populations passaged in T cell-deficient and immunocompetent mice, we found that the presence of T cells is associated with an increase in the diversity of the M. tuberculosis genome. Together, our findings put M. tuberculosis genetic evolution in a new perspective and clarify the impact of T cells on sequence diversity of M. tuberculosis.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Coscoll√°, Mireja and Gagneux, Sebastien
Item Type:Article, refereed
Publisher:Public Library of Science
ISSN:1553-7366
e-ISSN:1553-7374
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:13 Oct 2017 11:06
Deposited On:20 Apr 2017 12:28

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