Vattanaviboon Paiboon, Dulyayangkul Punyawee, Mongkolsuk Skorn, Charoenlap Nisanart
1Laboratory of Biotechnology, Chulabhorn Research Institute, Bangkok 10210, Thailand.
2Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok 10400, Thailand.
Acta Microbiol Immunol Hung. 2025 May 22;72(2):81-92. doi: 10.1556/030.2025.02578. Print 2025 Jun 20.
Stenotrophomonas maltophilia has emerged as an opportunistic pathogen originating from the environments, causing nosocomial infections, particularly in immunocompromised individuals and patients with cystic fibrosis. Although this microorganism exhibits low virulence, its infections are associated with high morbidity and mortality rates. S. maltophilia is intrinsically resistant to many antimicrobial agents used in clinical practices, therefore, posing significant treatment challenges. The multidrug resistance in S. maltophilia results from a combination of intrinsic, adaptive, and acquired mechanisms. S. maltophilia genome carries an array of genes encoding multidrug efflux pumps, which are key contributors to its broad-spectrum antibiotic resistance by expelling a wide range of drugs and reducing their intracellular concentrations to nontoxic levels. The majority of these efflux pumps belong to the resistance-nodulation-cell division (RND) family, while a lesser fraction is classified under the major facilitator superfamily (MFS) and the adenosine triphosphate binding cassette (ABC) family. In terms of function, substrate specificity, and complex gene regulation, these multidrug efflux pumps contribute not only to the survival of S. maltophilia under antibiotic stress but also to its resilience against other chemical challenges, including oxidative stress-generating substances and biocides. The roles of certain efflux pump systems in acquired and adaptive antibiotic resistance, as well as their potential applications as drug targets to enhance the efficacy of routinely used antibiotics through the use of small molecules capable of functioning as efflux pump inhibitors, are also discussed. A deeper understanding of these mechanisms can contribute to the more effective management against antibiotic-resistant S. maltophilia.
嗜麦芽窄食单胞菌已成为一种源自环境的机会致病菌，可引起医院感染，尤其是在免疫功能低下的个体和囊性纤维化患者中。尽管这种微生物的毒力较低，但其感染与高发病率和死亡率相关。嗜麦芽窄食单胞菌对临床实践中使用的许多抗菌药物具有内在抗性，因此带来了重大的治疗挑战。嗜麦芽窄食单胞菌的多重耐药性是由内在、适应性和获得性机制共同作用导致的。嗜麦芽窄食单胞菌的基因组携带一系列编码多药外排泵的基因，这些基因通过排出多种药物并将其细胞内浓度降低至无毒水平，从而成为其广谱抗生素抗性的关键因素。这些外排泵中的大多数属于耐药-结瘤-细胞分裂（RND）家族，而较小一部分则归类于主要易化子超家族（MFS）和三磷酸腺苷结合盒（ABC）家族。在功能、底物特异性和复杂的基因调控方面，这些多药外排泵不仅有助于嗜麦芽窄食单胞菌在抗生素压力下存活，还有助于其抵御其他化学挑战，包括产生氧化应激的物质和杀菌剂。还讨论了某些外排泵系统在获得性和适应性抗生素抗性中的作用，以及它们作为药物靶点的潜在应用，即通过使用能够作为外排泵抑制剂发挥作用的小分子来提高常规使用抗生素的疗效。对这些机制的更深入理解有助于更有效地应对耐抗生素的嗜麦芽窄食单胞菌。
