Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospitalgrid.278247.c, Taipei, Taiwan.
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0204321. doi: 10.1128/aac.02043-21. Epub 2022 Mar 14.
Pathogenic bacteria experience diverse stresses induced by host cells during infection and have developed intricate systems to trigger appropriate responses. Bacterial stress responses have been reported to defend against these stresses and cross-protect bacteria from antibiotic attack. In this study, we aimed to assess whether oxidative stress affects bacterial susceptibility to fluoroquinolone (FQ) and the underlying mechanism. Stenotrophomonas maltophilia, a species with high genetic diversity, is distributed ubiquitously and is an emerging multidrug-resistant opportunistic pathogen. FQs are among the limited antibiotic treatment options for S. maltophilia infection. The minimum inhibitory concentrations (MICs) of 103 S. maltophilia clinical isolates against ciprofloxacin (CIP) and levofloxacin (LVX) were determined using the agar dilution method in Mueller-Hinton plates with or without menadione (MD), a superoxide generator. The resistance rates for ciprofloxacin and levofloxacin were 40% and 18% in the MD-null group and increased to 91% and 23%, respectively, in the MD-treated group. Of the 103 isolates tested, 54% and 27% had elevated MICs against ciprofloxacin and levofloxacin, respectively, in the presence of MD. The involvement of oxidative stress responses in the MD-mediated FQ resistance was further assessed by mutants construction and viability assay. Among the 16 oxidative stress alleviation systems evaluated, and contributed to MD-mediated FQ resistance. The antibiotic susceptibility test is an accredited clinical method to evaluate bacterial susceptibility to antibiotics in clinical practice. However, oxidative stress-mediated antibiotic resistance was not detected using this test, which may lead to treatment failure.
在感染过程中，病原细菌会经历宿主细胞诱导的多种应激，并已发展出复杂的系统来触发适当的反应。据报道，细菌应激反应可抵御这些应激，并使细菌免受抗生素的攻击而产生交叉保护。在这项研究中，我们旨在评估氧化应激是否会影响细菌对氟喹诺酮（FQ）的敏感性及其潜在机制。嗜麦芽窄食单胞菌是一种遗传多样性很高的物种，分布广泛，是一种新兴的多药耐药机会性病原体。FQ 是治疗嗜麦芽窄食单胞菌感染的有限抗生素治疗选择之一。采用琼脂稀释法在 Mueller-Hinton 平板上测定了 103 株嗜麦芽窄食单胞菌临床分离株对环丙沙星（CIP）和左氧氟沙星（LVX）的最小抑菌浓度（MIC），平板中添加或不添加超氧化物生成剂甲萘醌（MD）。在无 MD 组中，对环丙沙星和左氧氟沙星的耐药率分别为 40%和 18%，而在 MD 处理组中，耐药率分别增加到 91%和 23%。在 103 株受试分离株中，分别有 54%和 27%的分离株在存在 MD 的情况下对环丙沙星和左氧氟沙星的 MIC 升高。通过突变体构建和生存力测定进一步评估了氧化应激反应在 MD 介导的 FQ 耐药中的作用。在所评估的 16 种氧化应激缓解系统中， 和 有助于 MD 介导的 FQ 耐药。抗生素药敏试验是一种临床认可的方法，用于评估临床实践中细菌对抗生素的敏感性。然而，这种试验未检测到氧化应激介导的抗生素耐药性，这可能导致治疗失败。
