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评估噬菌体-抗生素协同作用诱导鼠伤寒沙门氏菌产生交叉敏感性的潜力。

Assessment of the potential of phage-antibiotic synergy to induce collateral sensitivity in Salmonella Typhimurium.

机构信息

Department of Biomedical Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.

Department of Biomedical Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea; Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.

出版信息

Microb Pathog. 2023 Jul;180:106134. doi: 10.1016/j.micpath.2023.106134. Epub 2023 May 5.

DOI:10.1016/j.micpath.2023.106134
PMID:37150310
Abstract

This study was designed to evaluate the synergistic effect of phage and antibiotic on the induction of collateral sensitivity in Salmonella Typhimurium. The synergistic effects of Salmonella phage PBST32 combined with ciprofloxacin (CIP) against S. Typhimurium KCCM 40253 (ST) were evaluated using a fractional inhibitory concentration (FIC) assay. The CIP susceptibility of ST was increased when combined with PBST32, showing 16-fold decrease at 7 log PFU/mL. The combination of 1/2 × MIC of CIP and PBST32 (CIP[1/2]+PBST32) effectively inhibited the growth of ST up to below the detection limit (1.3 log CFU/mL) after 12 h of incubation at 37 °C. The significant reduction in bacterial swimming motility was observed for PBST32 and CIP[1/4]+PBST32. The CIP[1/4]+PBST32 increased the fitness cost (relative fitness = 0.57) and decreased the cross-resistance to different classes of antibiotics. ST treated with PBST32 alone treatment exhibited the highest coefficient of variation (90%), followed by CIP[1/4]+PBST32 (75%). These results suggest that the combination of PBST32 and CIP can be used to control bacterial pathogens.

摘要

本研究旨在评估噬菌体和抗生素对鼠伤寒沙门氏菌(Salmonella Typhimurium)诱导旁系敏感性的协同作用。采用部分抑菌浓度(FIC)测定法评估噬菌体 PBST32 与环丙沙星(CIP)联合对鼠伤寒沙门氏菌 KCCM 40253(ST)的协同作用。当与 PBST32 联合使用时,ST 的 CIP 敏感性增加,在 7 log PFU/mL 时表现出 16 倍的下降。CIP[1/2]与 PBST32 的组合(CIP[1/2]+PBST32)在 37°C 孵育 12 小时后,有效抑制 ST 的生长,使其低于检测限(1.3 log CFU/mL)。噬菌体 PBST32 和 CIP[1/4]+PBST32 显著降低了细菌游动能力。CIP[1/4]+PBST32 增加了适应性成本(相对适应性=0.57),并降低了对不同类别的抗生素的交叉耐药性。单独用 PBST32 处理的 ST 表现出最高的变异系数(90%),其次是 CIP[1/4]+PBST32(75%)。这些结果表明,PBST32 和 CIP 的联合使用可以用于控制细菌病原体。

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