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Transition bias influences the evolution of antibiotic resistance in Mycobacterium tuberculosis

Payne, Joshua L. and Menardo, Fabrizio and Trauner, Andrej and Borrell, Sonia and Gygli, Sebastian M. and Loiseau, Chloe and Gagneux, Sebastien and Hall, Alex R.. (2019) Transition bias influences the evolution of antibiotic resistance in Mycobacterium tuberculosis. PLoS Biology, 17 (5). e3000265.

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Official URL: https://edoc.unibas.ch/70514/

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Abstract

Transition bias, an overabundance of transitions relative to transversions, has been widely reported among studies of the rates and spectra of spontaneous mutations. However, demonstrating the role of transition bias in adaptive evolution remains challenging. In particular, it is unclear whether such biases direct the evolution of bacterial pathogens adapting to treatment. We addressed this challenge by analyzing adaptive antibiotic-resistance mutations in the major human pathogen Mycobacterium tuberculosis (MTB). We found strong evidence for transition bias in two independently curated data sets comprising 152 and 208 antibiotic-resistance mutations. This was true at the level of mutational paths (distinct adaptive DNA sequence changes) and events (individual instances of the adaptive DNA sequence changes) and across different genes and gene promoters conferring resistance to a diversity of antibiotics. It was also true for mutations that do not code for amino acid changes (in gene promoters and the 16S ribosomal RNA gene rrs) and for mutations that are synonymous to each other and are therefore likely to have similar fitness effects, suggesting that transition bias can be caused by a bias in mutation supply. These results point to a central role for transition bias in determining which mutations drive adaptive antibiotic resistance evolution in a key pathogen.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Menardo, Fabrizio and Trauner, Andrej and Borrell Farnov, Sonia and Gygli, Sebastian and Loiseau, ChloƩ Marie and Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1545-7885
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 May 2019 13:34
Deposited On:23 May 2019 13:34

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