Department of Civil and Environmental Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois United States.
Department of Chemical and Environmental Engineering, University of California, Riverside, California United States.
Environ Sci Technol. 2020 Jul 21;54(14):8770-8778. doi: 10.1021/acs.est.0c01155. Epub 2020 Jul 1.
Antibiotic resistance is one of the most challenging issues in public health. Antibiotics have been increasingly used not only for humans and animals but also for crop protection as pesticides. Thus, antibiotics often coexist with pesticides in some environments. To investigate the effects of the co-occurring, nonantibiotic pesticides on the development of antibiotic resistance, we conducted long-term exposure experiments using an 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.
抗生素耐药性是公共卫生领域面临的最具挑战性的问题之一。抗生素不仅越来越多地用于人类和动物，而且还被用作农药来保护农作物。因此，抗生素经常与农药共存于某些环境中。为了研究共存的非抗生素类农药对抗生素耐药性发展的影响，我们使用 K-12 模式菌株进行了长期暴露实验。结果表明：（1）单独暴露于农药（mg/L 水平）会导致对链霉素的耐药性显著提高的突变体的出现；（2）暴露于农药（μg/L 水平）与亚抑菌浓度（高μg/L 水平）的氨苄青霉素协同作用，刺激了氨苄青霉素耐药性和对其他抗生素（即环丙沙星、氯霉素和四环素）的交叉耐药性的选择。在同时暴露于农药和氨苄青霉素的选择压力下，耐药突变体中出现了明显不同且多样化的遗传突变。这些遗传突变可能导致在抗生素胁迫下的整体转录调控（例如生物膜形成、氧化应激防御），从而导致抗生素耐药性增加。总的来说，这些发现为在抗生素和非抗生素微污染物共存的环境相关条件下抗生素耐药性的发展和耐药机制提供了重要的基础见解。
