Conserved collateral susceptibility networks in diverse clinical strains of Escherichia coli
Dr. Nicole Podnecky, Elizabeth Fredheim, Julia Kloos, Vidar Sørum, Raul Primicerio, Adam Roberts, Dr. Daniel Rozen, Prof. Ørjan Samuelsen, Prof Pal Johnsen
Received: 23rd January 18
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, is a uniquely promising strategy that enables selection against resistance during treatment. However, using CS-informed therapy depends on conserved CS networks across genetically diverse bacterial strains. We examined CS conservation in diverse E. coli strains isolated from urinary tract infections. Collateral susceptibilities of mutants resistant to relevant antibiotics were determined against a panel of 16 antibiotics. Multivariate statistical results show that resistance mechanisms, in particular efflux-related mutations, as well as relative fitness were principal contributors to collateral responses. Moreover, collateral responses shifted the mutant selection window suggesting that CS-informed therapies could affect evolutionary trajectories of antimicrobial resistance. Our data allow optimism for CS-informed therapy and further suggest that early detection of resistance mechanisms is important to accurately predict collateral antimicrobial responses.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.