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

• DOI: 10.1038/s41467-018-06143-y
• Publication Date: 2018-09-04T13:55:47Z
• Authors: Nicole L. Podnecky; Elizabeth G. A. F...; Julia Kloos; Vidar Sørum; Raul Primicerio; Adam P. Roberts; Daniel E. Rozen; Ørjan Samuelsen; Pål J. Johnsen
• Keywords: Collateral damage; Efflux

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