Subinhibitory concentrations of nalidixic acid alter bacterial physiology and induce anthropogenic resistance in a commensal strain ofEscherichia coli in vitro

The human gut houses a complex group of bacterial genera, including both opportunistic pathogens and commensal micro‐organisms. These are regularly exposed to antibiotics, and their subinhibitory concentrations play a pivotal role in shaping the microbial responses. This study was aimed to investigate the effects exerted by sub‐MICs of nalidixic acid (NA) on the growth rate, bacterial motility, biofilm formation and expression of outer membrane proteins (OMPs) in a commensal strain of E. coli. The NA‐sensitive strain was sequentially passaged under sub‐MICs of NA. E‐test was used to determine the MIC values of NA. Results indicated significant changes in the growth profile of commensal E. coli upon exposure to NA at sub‐MICs. Differential expression of OMPs was observed in cells treated with sub‐MICs of NA. Bacterial motility was reduced under 1/2 MIC of NA. Interestingly, successive passaging under 1/2 MIC of NA led to the emergence of resistant E. coli with an increased MIC value of 64 µg ml−1 in just 24 days. The NA‐resistant variant was confirmed by comparing its 16S rRNA sequence to that of the sensitive commensal strain. Mutations in the Quinolone Resistance‐Determining Regions (QRDRs) of chromosomal gyrA, and Topoisomerase IV‐encoding parC genes were detected in NA‐resistant E. coli. Our results demonstrate how antibiotics play an important role as signalling molecules or elicitors in driving the pathogenicity of commensal bacteria in vitro.