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Mutational Pathway Determines Whether Drug Gradients Accelerate Evolution of Drug-Resistant Cells

Philip Greulich, Bartłomiej Waclaw, and Rosalind J. Allen
Phys. Rev. Lett. 109, 088101 – Published 20 August 2012
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Abstract

Drug gradients are believed to play an important role in the evolution of bacteria resistant to antibiotics and tumors resistant to anticancer drugs. We use a statistical physics model to study the evolution of a population of malignant cells exposed to drug gradients, where drug resistance emerges via a mutational pathway involving multiple mutations. We show that a nonuniform drug distribution has the potential to accelerate the emergence of resistance when the mutational pathway involves a long sequence of mutants with increasing resistance, but if the pathway is short or crosses a fitness valley, the evolution of resistance may actually be slowed down by drug gradients. These predictions can be verified experimentally, and may help to improve strategies for combating the emergence of resistance.

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  • Received 2 March 2012

DOI:https://doi.org/10.1103/PhysRevLett.109.088101

© 2012 American Physical Society

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Bacteria Evolve to Go Against the Grain

Published 20 August 2012

Drug gradients may give bacteria an evolutionary boost towards antibiotic resistance.

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Authors & Affiliations

Philip Greulich, Bartłomiej Waclaw, and Rosalind J. Allen

  • SUPA, School of Physics and Astronomy, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JZ, United Kingdom

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Issue

Vol. 109, Iss. 8 — 24 August 2012

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