Antibiotic collateral sensitivity is contingent on the repeatability of evolution.

ABSTRACT: Antibiotic resistance represents a growing health crisis that necessitates the immediate discovery of novel treatment strategies. One such strategy is the identification of collateral sensitivities, wherein evolution under a first drug induces susceptibility to a second. Here, we report that sequential drug regimens derived from in vitro evolution experiments may have overstated therapeutic benefit, predicting a collaterally sensitive response where cross-resistance ultimately occurs. We quantify the likelihood of this phenomenon by use of a mathematical model parametrised with combinatorially complete fitness landscapes for Escherichia coli. Through experimental evolution we then verify that a second drug can indeed stochastically exhibit either increased susceptibility or increased resis

SUBMITTER: Nichol D 

PROVIDER: S-EPMC6338734 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature