Exposure to Environmental Levels of Pesticides Stimulates and Diversifies Evolution in Escherichia coli toward Higher Antibiotic Resistance

K-12 model strain. The results reveal that (1) the exposure to pesticides (in mg/L) alone led to the emergence of mutants with significantly higher resistance to streptomycin; (2) the exposure to pesticides (in μg/L) together with a subinhibitory level (in high μg/L) of ampicillin synergistically stimulated the selection of ampicillin resistance and the cross-resistance to other antibiotics (i.e., ciprofloxacin, chloramphenicol, and tetracycline). Distinct and diversified genetic mutations emerged in the resistant mutants selected from the coexposure to both pesticides and ampicillin. The genetic mutations likely caused a holistic transcriptional regulation (e.g., biofilm formation, oxidative stress defense) when grown under antibiotic stress and led to increased antibiotic resistance. Together, these findings provide important fundamental insights into the development of antibiotic resistance and the resistance mechanisms under environmentally relevant conditions where antibiotics and nonantibiotic micropollutants coexist.