Journal article
Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity
PLoS pathogens, Vol.12(12), pp.e1006111-e1006111
12/2016
Handle:
https://hdl.handle.net/2376/100245
PMCID: PMC5189959
PMID: 27973588
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.
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Details
- Title
- Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity
- Creators
- Richard Copin - Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY, United States of AmericaXueying Wang - Department of Mathematics and Statistics, Washington State University, Pullman, WA, United States of AmericaEddie Louie - Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY, United States of AmericaVincent Escuyer - Microbiology laboratory, Wadsworth Center, New York State Department of Health, Albany, NY, United States of AmericaMireia Coscolla - University of Basel, Basel, SwitzerlandSebastien Gagneux - University of Basel, Basel, SwitzerlandGuy H Palmer - Paul G. Allen School for Global Animal Health, Washington State University, Pullman, WA, United States of AmericaJoel D Ernst - Department of Pathology, New York University School of Medicine, New York, NY, United States of America
- Publication Details
- PLoS pathogens, Vol.12(12), pp.e1006111-e1006111
- Academic Unit
- Mathematics and Statistics, Department of; Paul G. Allen School for Global Animal Health
- Publisher
- United States
- Grant note
- R01 AI090928 / NIAID NIH HHS U19 AI111211 / NIAID NIH HHS
- Identifiers
- 99900546661301842
- Language
- English
- Resource Type
- Journal article