TY - JOUR T1 - The Role of Compensatory Mutations in the Emergence of Drug Resistance A1 - Handel, Andreas A1 - Regoes, Roland R A1 - Antia, Rustom Y1 - 2006/10/13 N2 - 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. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 2 IS - 10 UR - https://doi.org/10.1371/journal.pcbi.0020137 SP - e137 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.0020137 ER -