Antibiotic collateral sensitivity is contingent on the repeatability of evolution.

Antibiotic collateral sensitivity is contingent on the repeatability of evolution. Nat Commun. 2019 Jan 18;10(1):334 Authors: Nichol D, Rutter J, Bryant C, Hujer AM, Lek S, Adams MD, Jeavons P, Anderson ARA, Bonomo RA, Scott JG 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 resistance when following a first. Genetic divergence is confirmed as the driver of this differential response through targeted and whole genome sequencing. Taken together, these results highlight that the success of evolutionarily-informed therapies is predicated on a rigorous probabilistic understanding of the contingencies that arise during the evolution of drug resistance. PMID: 30659188 [PubMed - in process]
Source: Genomics Proteomics ... - Category: Genetics & Stem Cells Authors: Tags: Nat Commun Source Type: research