The Role of Compensatory Mutations in the Emergence of Drug Resistance

• Type of Material: Article
• Authors: Andreas Handel, Emory University; Roland R Roland R, Emory University; Rustom Antia, Emory University
• Language: English
• Date: 2006-10
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2006 Handel et al.
• Final Published Version (URL): http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.0020137
• Title of Journal or Parent Work: PLoS Computational Biology
• ISSN: 1553-734X
• Volume: 2
• Issue: 10
• Start Page: e137
• End Page: e137
• Grant/Funding Information: We acknowledge funding by the National Institute of General Medical Sciences of the (US) National Institutes of Health.
• Research Categories: Health Sciences, Toxicology; Health Sciences, Epidemiology; Health Sciences, Pathology

Abstract

Pathogens that evolve resistance to drugs usually have reduced fitness. However, mutations that largely compensate for this reduction in fitness often arise. We investigate how these compensatory mutations affect population-wide resistance emergence as a function of drug treatment. Using a model of gonorrhea transmission dynamics, we obtain generally applicable, qualitative results that show how compensatory mutations lead to more likely and faster resistance emergence. We further show that resistance emergence depends on the level of drug use in a strongly nonlinear fashion. We also discuss what data need to be obtained to allow future quantitative predictions of resistance emergence.