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PLoS Comput Biol. 2006 Oct;2(10):e137.

The role of compensatory mutations in the emergence of drug resistance.

Author information

1
Department of Biology, Emory University, Atlanta, Georgia, United States of America. ahandel@emory.edu

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.

PMID:
17040124
PMCID:
PMC1599768
DOI:
10.1371/journal.pcbi.0020137
[Indexed for MEDLINE]
Free PMC Article

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