Collateral sensitivity in clinical Escherichia coli isolates

Abstract

The continuous increase in resistance development towards antimicrobial agents is a well-known problem, however, insecurities exist about how frequently the emergence of resistance in microbes, at the same time, leads to an increased sensitivity to other antimicrobial agents. This phenomenon is called “collateral sensitivity”. We evolved resistance in clinical E. coli strains towards three antimicrobial drugs used clinically in the treatment of urinary tract infections to determine collateral effects towards selected antibiotics. The collateral effects were confirmed by determination of changes in susceptibility by performing E-tests. The resulting collateral sensitivity and resistance profiles were mapped to see if there existed a network or general pattern of collateral sensitivity. The results predominantly showed a higher level of collateral sensitivity between resistant mutants and drug with an increase in minimum inhibiotiry concentration (MIC) up to 32-fold for the mutant compared to its respective wild type. A low level of collateral resistance was also observed, but collateral sensitivity was observed to a greater extent than collateral resistance. Overall, our project supported a general pattern for the different E. coli resistant isolates. This project provides a proof-of-principle of the phenomenon “collateral sensitivity” and can thus contribute to sustainable use of antimicrobials clinically by slowing down the rate of resistance evolution.