Department of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
Future Food Laboratory, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314100, China.
FEMS Microbiol Lett. 2024 Jan 9;371. doi: 10.1093/femsle/fnae050.
This study was designed to evaluate the history-dependent behaviors of Salmonella Typhimurium re-exposed to sublethal levels of ciprofloxacin. The S. Typhimurium cells were pre-exposed to 0 (CON), 1/16 (LOW), 1/8 (MED), and 1/4 (HIGH) minimum inhibitory concentrations (MICs) of ciprofloxacin, followed by re-exposure to the same concentrations. The bacterial growth, postantibiotic effect (PAE), relative fitness, and swimming motility of treatments were evaluated in the absence of ciprofloxacin. The lag phase duration (LPD) was estimate to assess bacterial recovery under ciprofloxacin exposure. A disk diffusion assay was used to determine the cross-resistance and collateral sensitivity of CON, LOW, MED, and HIGH treatments to ciprofloxacin (CIP), ceftriaxone (CEF), erythromycin (ERY), gentamicin (GEN), and polymyxin B (POL). The S. Typhimurium cells pre-exposed to ciprofloxacin were susceptible in antibiotic-free media, showing delayed growth. The highest PAE (>1 h) and bacterial fluctuation (CV = 5%) were observed at the High treatment compared to the CON. The HIGH treatment had the lowest relative fitness levels (0.87) and swimming motility (55 mm). The LPD was significantly decreased at the LOW treatment (1.8 h) when re-exposed to 1/16 × MIC of ciprofloxacin. The LOW, MED, and HIGH treatments showed the cross-resistance to POL and the collateral sensitivity to CEF, ERY, and GEN. The pre-exposure to ciprofloxacin could induce phenotypic diversity, corresponding to the history-dependent behaviors. These results provide important insights for the dynamic nature of bacterial populations when re-exposed to sublethal concentrations of antibiotics.
本研究旨在评估伤寒沙门氏菌重新暴露于亚致死浓度环丙沙星时的时依性行为。将伤寒沙门氏菌细胞预先暴露于 0（对照）、1/16（低）、1/8（中）和 1/4（高）最小抑菌浓度（MIC）的环丙沙星中，然后再暴露于相同浓度。在不存在环丙沙星的情况下，评估了细菌生长、抗生素后效应（PAE）、相对适应性和泳动性。通过估计迟滞期持续时间（LPD）来评估细菌在环丙沙星暴露下的恢复情况。采用圆盘扩散法测定对照（CON）、低（LOW）、中（MED）和高（HIGH）处理对环丙沙星（CIP）、头孢曲松（CEF）、红霉素（ERY）、庆大霉素（GEN）和多粘菌素 B（POL）的交叉耐药性和附带敏感性。预先暴露于环丙沙星的伤寒沙门氏菌细胞在无抗生素的培养基中敏感，表现出生长延迟。与对照相比，HIGH 处理表现出最高的 PAE（>1 小时）和细菌波动（CV=5%）。HIGH 处理的相对适应性水平（0.87）和泳动性（55 毫米）最低。当重新暴露于 1/16×MIC 的环丙沙星时，LOW 处理的 LPD 显著降低（1.8 小时）。LOW、MED 和 HIGH 处理对 POL 表现出交叉耐药性，对 CEF、ERY 和 GEN 表现出附带敏感性。预先暴露于环丙沙星可以诱导表型多样性，与时依性行为相对应。这些结果为细菌种群重新暴露于亚致死浓度抗生素时的动态性质提供了重要的见解。
