Abstract

Infections caused by antibiotic-resistant bacteria lead to millions of deaths each year and pose a significant challenge to healthcare systems. There is an urgent need for new antibiotics or strategies to combat antibiotic resistance. Reduced glutathione (GSH) is a naturally occurring thiol compound, and the balance between its reduced form (GSH) and its oxidized form (GSSG) is crucial for maintaining optimal intracellular redox potential, which is essential for various normal cellular processes. In my laboratory, we have investigated the effects of both intracellular and extracellular GSH on Gram-negative bacteria, including Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Our findings demonstrate that: i) intracellular GSH is linked to antibiotic susceptibility, ii) extracellular GSH shows antibacterial activity regardless of whether the bacteria are susceptible or resistant to antibiotics, iii) the antibacterial effect of GSH enhances the susceptibility of bacteria to traditional antibiotics, and iv) GSH-mediated acidity is partially related to its antibacterial properties. These results suggest that GSH could be a promising alternative approach for treating multidrug-resistant Gram-negative bacterial infections.