Kok Maik, van Os Wisse, Hankemeier Thomas, van Hasselt J G Coen
Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
FEMS Microbiol Lett. 2025 Jan 10;372. doi: 10.1093/femsle/fnaf066.
Chronic respiratory tract infections with Pseudomonas aeruginosa frequently occur in patients with cystic fibrosis, chronic obstructive pulmonary disease, and bronchiectasis. A hallmark of these conditions is the accumulation of mucus plugs, creating oxygen-limited niches. Within these microenvironments, P. aeruginosa undergoes cellular modifications that may alter its antibiotic sensitivity. Although the acute effects of anoxia are well studied, the impact of prolonged anoxic exposure on antibiotic sensitivity remains unclear. In this study, we developed anoxic-conditioned P. aeruginosa strains by passaging a laboratory strain for 22 days in an anoxic environment. We performed time-kill assays with both parental and anoxic-conditioned strains in anoxic and aerobic environments, using ceftazidime, ciprofloxacin, colistin, and tobramycin. The anoxic-conditioned strains exhibited increased susceptibility to tobramycin and reduced sensitivity to colistin and ceftazidime. These differences were attributed to altered killing rates (as with tobramycin) or reduced regrowth under anoxic conditions (as with colistin). For ciprofloxacin, a steeper killing rate was observed against the anoxic-conditioned strains, but 24-h outcomes were similar to the parental strain. Overall, our findings demonstrate that long-term anoxia alters antibiotic sensitivity in P. aeruginosa differently than acute anoxia, with important implications for treating chronic infections in oxygen-limited environments.
铜绿假单胞菌引起的慢性呼吸道感染常见于囊性纤维化、慢性阻塞性肺疾病和支气管扩张症患者。这些病症的一个标志是黏液栓的积聚，形成缺氧微环境。在这些微环境中，铜绿假单胞菌会发生细胞变化，这可能会改变其对抗生素的敏感性。尽管缺氧的急性影响已得到充分研究，但长期缺氧暴露对抗生素敏感性的影响仍不清楚。在本研究中，我们通过在缺氧环境中将一株实验室菌株传代培养22天，构建了缺氧适应型铜绿假单胞菌菌株。我们使用头孢他啶、环丙沙星、黏菌素和妥布霉素，在缺氧和好氧环境中对亲本菌株和缺氧适应型菌株进行了时间杀菌试验。缺氧适应型菌株对妥布霉素的敏感性增加，对黏菌素和头孢他啶的敏感性降低。这些差异归因于杀菌速率的改变（如妥布霉素）或缺氧条件下再生长的减少（如黏菌素）。对于环丙沙星，观察到对缺氧适应型菌株的杀菌速率更陡，但24小时的结果与亲本菌株相似。总体而言，我们的研究结果表明，长期缺氧与急性缺氧不同，它会改变铜绿假单胞菌的抗生素敏感性，这对治疗缺氧环境中的慢性感染具有重要意义。
