Pathogenic Escherichia coli Possess Elevated Growth Rates under Exposure to Sub-Inhibitory Concentrations of Azithromycin

Abstract

Antimicrobial resistance (AMR) has been identified by the World Health Organization (WHO) as one of the ten major threats to global health. Advances in technology, including whole-genome sequencing, have provided new insights into the origin and mechanisms of AMR. However, our understanding of the short-term impact of antimicrobial pressure and resistance on the physiology of bacterial populations is limited. We aimed to investigate morphological and physiological responses of clinical isolates of E. coli under short-term exposure to key antimicrobials. We performed whole-genome sequencing on twenty-seven E. coli isolates isolated from children with sepsis to evaluate their AMR gene content. We assessed their antimicrobial susceptibility profile and measured their growth dynamics and morphological characteristics under exposure to varying concentrations of ciprofloxacin, ceftriaxone, tetracycline, gentamicin, and azithromycin. AMR was common, with all organisms resistant to at least one antimicrobial; a total of 81.5% were multi-drug-resistant (MDR). We observed an association between resistance profile and morphological characteristics of the E. coli over a three-hour exposure to antimicrobials. Growth dynamics experiments demonstrated that resistance to tetracycline promoted the growth of E. coli under antimicrobial-free conditions, while resistance to the other antimicrobials incurred a fitness cost. Notably, antimicrobial exposure heterogeneously suppressed bacterial growth, but sub-MIC concentrations of azithromycin increased the maximum growth rate of the clinical isolates. Our results outline complex interactions between organism and antimicrobials and raise clinical concerns regarding exposure of sub-MIC concentrations of specific antimicrobials.