Kwon Dong H, Almansour Ayidh, Alharbe Roaa
Department of Natural and Life Sciences, Long Island University, 1 University Plaza, Brooklyn, NY, 11201, USA.
Saudi Food and Drug Authority, Riyadh, Saudi Arabia.
Biochem Biophys Res Commun. 2025 Sep 1;777:152307. doi: 10.1016/j.bbrc.2025.152307. Epub 2025 Jul 4.
Acinetobacter baumannii (A. baumannii) is a Gram-negative bacterial pathogen that causes infections in the lungs, bloodstream, urinary tract, and wounds. This bacterium has become one of the most challenging pathogens for healthcare institutions worldwide. A big problem in treating these infections is that oxacillinase (OXA)-type carbapenemase-producing A. baumannii often resists many antibiotics that are not β-lactams, including almost all β-lactams. Glutathione is a tripeptide (l-glutathione, l-cysteine, and l-glycine) antioxidant synthesized in most Gram-negative bacteria and eukaryotic cells. Exogenous glutathione has been evaluated for antibacterial properties and various clinical implications. A previous study showed that exogenous glutathione significantly enhanced the susceptibility of β-lactam antibiotics in OXA-type carbapenemase-producing A. baumannii. However, the effect of exogenous glutathione on non-β-lactam antibiotics was unclear. In this study, the antibacterial activity of exogenous glutathione against A. baumannii was determined at various concentrations. Additionally, the effect of exogenous glutathione on several non-β-lactam antibiotics, including chloramphenicol, ciprofloxacin, erythromycin, novobiocin, kanamycin, and tetracycline, was evaluated on four OXA-type carbapenemase-producing strains of A. baumannii: bla, bla, bla, and bla. The results showed that exogenous glutathione significantly inhibited bacterial growth at concentrations greater than 10 mM, achieving complete growth inhibited at 16 mM. Interestingly, at the subinhibitory concentration of 10 mM, exogenous glutathione increased susceptibility (more sensitive) to chloramphenicol, novobiocin, and tetracycline by as much as 256-fold. Conversely, it decreased susceptibility (more resistant) to ciprofloxacin, erythromycin, and kanamycin by up to 32-fold at the same subinhibitory concentration. These findings highlight the need for caution when using glutathione in combination with antibiotics, especially for treating A. baumannii infections.
鲍曼不动杆菌是一种革兰氏阴性细菌病原体，可引起肺部、血液、泌尿道和伤口感染。这种细菌已成为全球医疗机构面临的最具挑战性的病原体之一。治疗这些感染的一个大问题是，产奥沙西林酶（OXA）型碳青霉烯酶的鲍曼不动杆菌通常对许多非β-内酰胺类抗生素耐药，包括几乎所有的β-内酰胺类抗生素。谷胱甘肽是一种三肽（L-谷胱甘肽、L-半胱氨酸和L-甘氨酸）抗氧化剂，在大多数革兰氏阴性细菌和真核细胞中合成。外源性谷胱甘肽已被评估其抗菌特性和各种临床意义。先前的一项研究表明，外源性谷胱甘肽可显著增强产OXA型碳青霉烯酶的鲍曼不动杆菌对β-内酰胺类抗生素的敏感性。然而，外源性谷胱甘肽对非β-内酰胺类抗生素的作用尚不清楚。在本研究中，测定了不同浓度的外源性谷胱甘肽对鲍曼不动杆菌的抗菌活性。此外，在四株产OXA型碳青霉烯酶的鲍曼不动杆菌（bla、bla、bla和bla）上评估了外源性谷胱甘肽对几种非β-内酰胺类抗生素的影响，包括氯霉素、环丙沙星、红霉素、新生霉素、卡那霉素和四环素。结果表明，外源性谷胱甘肽在浓度大于10 mM时显著抑制细菌生长，在16 mM时实现完全生长抑制。有趣的是，在10 mM的亚抑菌浓度下，外源性谷胱甘肽使对氯霉素、新生霉素和四环素的敏感性（更敏感）提高了多达256倍。相反，在相同的亚抑菌浓度下，它使对环丙沙星、红霉素和卡那霉素的敏感性（更耐药）降低了多达32倍。这些发现强调了在将谷胱甘肽与抗生素联合使用时，尤其是治疗鲍曼不动杆菌感染时需要谨慎。
