Kwon Dong H, Vasoya Mital, Sankaranarayanan Danya
Department of Natural and Life Sciences, Long Island University, Brooklyn, NY, USA.
J Antibiot (Tokyo). 2025 Jul 14. doi: 10.1038/s41429-025-00850-7.
Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and Pseudomonas aeruginosa, associated with systemic and hospital-acquired infections, have spread globally and pose a significant public health concern. Glutathione is a multifunctional thiol-antioxidant compound synthesized in most Gram-negative bacteria and crucial in maintaining intracellular redox homeostasis. Exogenous glutathione exhibits antibiotic properties and has differential effects on conventional antibiotics. Therefore, its effect on specific antibiotics needs to be clarified in bacterial species. In this study, we investigated the antibacterial activity of glutathione and its effect on meropenem susceptibility in KPC-producing bacteria. Two major KPC-encoding genes cloned from two different clinical KPC-producing K. pneumoniae were introduced into E. coli and P. aeruginosa. Then, the KPC-producing K. pneumoniae, E. coli, and P. aeruginosa were used for minimum inhibitory concentration (MIC), population analysis, checkerboard, and time-killing assays. The results showed that glutathione exhibited antibacterial activity at >10 mM in K. pneumoniae, E. coli, and P. aeruginosa. MIC levels of meropenem combined with 10 mM of glutathione were synergistically decreased by 8- to ≥ 256-fold in KPC-producing bacteria. Furthermore, this combination killed 100% of the KPC-producing bacteria at 2 to 4 μg mL of meropenem. These findings suggest that exogenous glutathione may be applicable in fighting infections caused by KPC-producing bacteria.
产肺炎克雷伯菌碳青霉烯酶（KPC）的肠杆菌科细菌和铜绿假单胞菌与全身性感染和医院获得性感染相关，已在全球范围内传播，引起了重大的公共卫生关注。谷胱甘肽是一种在大多数革兰氏阴性细菌中合成的多功能硫醇抗氧化化合物，对维持细胞内氧化还原稳态至关重要。外源性谷胱甘肽具有抗生素特性，对传统抗生素有不同的作用。因此，其对特定抗生素的作用需要在细菌物种中加以阐明。在本研究中，我们研究了谷胱甘肽的抗菌活性及其对产KPC细菌美罗培南敏感性的影响。从两种不同临床产KPC的肺炎克雷伯菌中克隆的两个主要KPC编码基因被导入大肠杆菌和铜绿假单胞菌。然后，将产KPC的肺炎克雷伯菌、大肠杆菌和铜绿假单胞菌用于最低抑菌浓度（MIC）、群体分析、棋盘法和时间杀菌试验。结果表明，谷胱甘肽在肺炎克雷伯菌、大肠杆菌和铜绿假单胞菌中浓度>10 mM时表现出抗菌活性。在产KPC细菌中，美罗培南与10 mM谷胱甘肽联合使用时，MIC水平协同降低了8至≥256倍。此外，这种联合用药在美罗培南浓度为2至4μg/mL时可杀死100%的产KPC细菌。这些发现表明，外源性谷胱甘肽可能适用于对抗由产KPC细菌引起的感染。
