Journal
PLOS COMPUTATIONAL BIOLOGY
Volume 2, Issue 10, Pages 1262-1270Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pcbi.0020137
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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.
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