摘要

本研究旨在评价联合应用抗生素治疗伤寒沙门氏菌的耐药性演变。用单一抗生素（卡那霉素，kan；青霉素，pen；红霉素，ery）或两种抗生素（kan+pen或kan+ery）联合应用（通过分数抑制浓度（fics）、逐步抗性选择、交叉抗性评价）评价鼠伤寒沙门氏菌耐药性的实验进展。抗性适应性和相对基因表达。Kan+Pen和Kan+Ery对鼠伤寒杆菌有协同作用（FIC指数<0.5）。Kan+ery延迟了鼠伤寒沙门氏菌新突变的诱导。仅在Kan和Pen中观察到鼠伤寒杆菌对红霉素和四环素以外的所有抗生素的交叉耐药性。单次抗生素治疗的适合度成本低于联合治疗。PEN的相对适应度最高为0.91，其次是Kan（0.84）和Ery（0.78），表明单一抗生素治疗的适应度成本较低。在单次抗生素治疗中观察到外排泵相关基因（ACRA和ACRB）、外膜相关基因（OMPC）和粘附相关基因（CSGD）的过度表达。我们的研究结果表明，Kan+Pen和Kan+Ery可以通过减少鼠伤寒杆菌的耐药性演变和重复使用传统抗生素来作为一种潜在的治疗方法。

This study was designed to evaluate the evolution of antibiotic resistance in Salmonella enterica serovar Typhimurium treated with the combination of antibiotics. The experimental evolution of antibiotic resistance of S. Typhimurium was evaluated either under single antibiotic (kanamycin, KAN; penicillin, PEN; erythromycin, ERY) or in combination of two antibiotics (KAN + PEN or KAN + ERY) as measured by fractional inhibitory concentrations (FICs), stepwise resistance selection, cross-resistance evaluation, resistance fitness, and relative gene expression. KAN + PEN and KAN + ERY showed the synergistic effect against S. Typhimurium (FIC index < 0.5). KAN + ERY delayed the induction of de novo mutations in S. Typhimurium. The cross-resistance of S. Typhimurium to all antibiotics except erythromycin and tetracycline was observed in KAN and PEN alone. The fitness cost was lower in single antibiotic treatments than combinations. The highest relative fitness was 0.91 in PEN, followed by KAN (0.84) and ERY (0.78), indicating the low fitness costs in single antibiotic treatments. The overexpression of efflux pump-related genes (acrA and acrB), outer membrane-related gene (ompC), and adherence-related gene (csgD) were observed in the single antibiotic treatments. Our results suggest that KAN + PEN and KAN + ERY could be used as a potential therapeutic treatment by decreasing the evolution of antibiotic resistance in S. Typhimurium and reusing conventional antibiotics.

https://www.ncbi.nlm.nih.gov/pubmed/31183498