A major clinical impact of A. baumannii is hospital-acquired infections including ventilator-associated pneumonia. The treatment of this pathogen is often difficult due to its innate and acquired resistance to almost all commercially available antibiotics. Infections with carbapenem-associated multidrug resistant A. baumannii is the most problematic. Glutathione is a tripeptide thiol-antioxidant and antibacterial activity of exogenous glutathione was reported in some bacteria. However, clinical relevance and molecular details of the antibacterial activity of glutathione are currently unclear. Seventy clinical isolates of A. baumannii including 63 carbapenem-associated multidrug resistant isolates and a type strain A. baumannii ATCC 19606 were used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Fractional inhibitory concentration (FIC) and time-killing activity with meropenem and/or glutathione were also determined in the carbapenem-associated multidrug resistant isolates. In addition, the roles of exogenous glutathione in multidrug efflux pumps and β-lactamase production were examined. Levels of MIC and MBC were ranged from 10 to 15mM of exogenous glutathione. All tested carbapenem-associated multidrug resistant isolates were sensitized by all tested antibiotics in combination with subinhibitory concentrations of glutathione. FIC levels of glutathione with carbapenem (meropenem) were all<0.5 and the carbapenem-associated multidrug resistant isolates were killed by subinhibitory concentrations of both glutathione and meropenem at>2log10 within 12h, suggesting glutathione synergistically interacts with meropenem. The roles of multidrug efflux pumps and β-lactamase production were excluded for the glutathione-mediated antibiotic susceptibility. Overall results demonstrate that the antibacterial activity of glutathione is clinically relevant and its synergism on antibiotics sensitizes clinical isolates of A. baumannii regardless of their resistance or susceptibility to antibiotics. This finding suggests that exogenous glutathione alone and/or in combination with existing antibiotics may be applicable to treat infections with carbapenem-associated multidrug resistant A. baumannii.

中文翻译：

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外源性谷胱甘肽的抗菌活性及其对抗生素的增效作用使碳青霉烯相关的多重耐药鲍曼不动杆菌临床分离株敏感。

鲍曼不动杆菌的主要临床影响是医院获得性感染，包括呼吸机相关性肺炎。由于这种病原体对几乎所有市售抗生素具有先天和后天的抵抗力，因此通常难以治疗。与碳青霉烯相关的多重耐药性鲍曼不动杆菌的感染是最成问题的。谷胱甘肽是一种三肽硫醇抗氧化剂，在某些细菌中据报道外源性谷胱甘肽具有抗菌活性。然而，目前尚不清楚谷胱甘肽的抗菌活性的临床相关性和分子细节。七十个鲍曼不动杆菌临床分离株，包括63个与碳青霉烯相关的多药耐药菌株和一株鲍曼不动杆菌ATCC 19606型菌株，被用于确定最小抑菌浓度（MIC）和最小杀菌浓度（MBC）。在与碳青霉烯有关的多重耐药菌株中，还测定了美罗培南和/或谷胱甘肽的分数抑制浓度（FIC）和杀灭时间。此外，检查了外源性谷胱甘肽在多药外排泵中的作用和β-内酰胺酶的产生。MIC和MBC的水平为10至15mM的外源性谷胱甘肽。所有测试的与碳青霉烯有关的耐多药分离株均通过所有测试的抗生素与亚抑制浓度的谷胱甘肽联合致敏。FIC的谷胱甘肽与碳青霉烯（美洛培南）的含量均<0.5，且与碳青霉烯相关的多药耐药菌株在12h内被亚抑制浓度的谷胱甘肽和美洛培南的浓度均> 2log10杀死，表明谷胱甘肽与美罗培南协同相互作用。对于谷胱甘肽介导的抗生素敏感性，排除了多药外排泵和β-内酰胺酶产生的作用。总体结果表明，谷胱甘肽的抗菌活性在临床上具有相关性，并且其与抗生素的协同作用使鲍曼不动杆菌的临床分离株变得敏感，无论其对抗生素的耐药性或敏感性如何。该发现表明，单独和/或与现有抗生素组合的外源性谷胱甘肽可适用于治疗与碳青霉烯相关的多重耐药鲍曼不动杆菌的感染。鲍曼氏菌，无论其对抗生素的耐药性或敏感性。该发现表明，单独和/或与现有抗生素组合的外源性谷胱甘肽可适用于治疗与碳青霉烯相关的多重耐药鲍曼不动杆菌的感染。鲍曼氏菌，无论其对抗生素的耐药性或敏感性。该发现表明，单独和/或与现有抗生素组合的外源性谷胱甘肽可适用于治疗与碳青霉烯相关的多重耐药鲍曼不动杆菌的感染。