Quantifying the Determinants of Evolutionary Dynamics Leading to Drug Resistance.

ABSTRACT: The emergence of drug resistant pathogens is a serious public health problem. It is a long-standing goal to predict rates of resistance evolution and design optimal treatment strategies accordingly. To this end, it is crucial to reveal the underlying causes of drug-specific differences in the evolutionary dynamics leading to resistance. However, it remains largely unknown why the rates of resistance evolution via spontaneous mutations and the diversity of mutational paths vary substantially between drugs. Here we comprehensively quantify the distribution of fitness effects (DFE) of mutations, a key determinant of evolutionary dynamics, in the presence of eight antibiotics representing the main modes of action. Using precise high-throughput fitness measurements for genome-wide Escherichia c

SUBMITTER: Chevereau G 

PROVIDER: S-EPMC4651364 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature