Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli.

Podnecky, Nicole L, Fredheim, Elizabeth G A, Kloos, Julia, Sørum, Vidar, Primicerio, Raul, Roberts, Adam ORCID: https://orcid.org/0000-0002-0760-3088, Rozen, Daniel E, Samuelsen, Ørjan and Johnsen, Pål J (2018) 'Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli.'. Nature Communications, Vol 9, Issue 1, p. 3673.

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Abstract

There is urgent need to develop novel treatment strategies to reduce antimicrobial resistance. Collateral sensitivity (CS), where resistance to one antimicrobial increases susceptibility to other drugs, might enable selection against resistance during treatment. However, the success of this approach would depend on the conservation of CS networks across genetically diverse bacterial strains. Here, we examine CS conservation across diverse Escherichia coli strains isolated from urinary tract infections. We determine collateral susceptibilities of mutants resistant to relevant antimicrobials against 16 antibiotics. Multivariate statistical analyses show that resistance mechanisms, in particular efflux-related mutations, as well as the relative fitness of resistant strains, are principal contributors to collateral responses. Moreover, collateral responses shift the mutant selection window, suggesting that CS-informed therapies may affect evolutionary trajectories of antimicrobial resistance. Our data allow optimism for CS-informed therapy and further suggest that rapid detection of resistance mechanisms is important to accurately predict collateral responses.

Item Type:	Article
Subjects:	QV Pharmacology > Anti-Bacterial Agents. Tissue Extracts > QV 350 Anti-bacterial agents (General or not elsewhere classified) QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified. WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 290 Escherichia coli infections WJ Urogenital System > WJ 151 Urinary tract infections
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/s41467-018-06143-y
Depositing User:	Stacy Murtagh
Date Deposited:	19 Sep 2018 08:34
Last Modified:	19 Sep 2018 08:34
URI:	https://archive.lstmed.ac.uk/id/eprint/9341

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