The Effects of Exogenous Glutathione on β-lactam Susceptibility in New Delhi Metallo-β-Lactamase (NDM-1) Producing Klebsiella pneumoniae.

The global spread of NDM-1-producing Klebsiella pneumoniae poses a serious therapeutic challenge because these strains are resistant to nearly all β-lactams and many other antibiotics. Glutathione (GSH) is essential for maintaining intracellular redox homeostasis, thereby protecting cells from oxidative damage. However, exogenous GSH may disrupt this homeostasis and increase bacterial vulnerability to oxidative stress, such as that induced by antibiotic exposure. This study investigates whether exogenous GSH exerts antibacterial activity and increases β-lactam susceptibility in NDM-1-producing K. pneumoniae ATCC BAA-2146, with potential implications for improved treatment strategies. Exogenous GSH inhibited the growth of NDM-1-producing K. pneumoniae at 5 and 10 mM. HCl-adjusted media matching the acidity of 10 mM GSH (pH 5.2 ± 0.1), but not 5 mM (pH 6.1 ± 0.1), similarly inhibited bacterial growth. Meropenem MICs decreased from 32 to 1 µg/mL with 5 mM GSH and to 8 µg/mL under matched acidity. Both 10 mM GSH and matched acidity decreased meropenem MICs from 32 to ≤ 0.25 µg/mL. For aztreonam, carbenicillin, and ceftazidime, 10 mM GSH decreased MICs 4-fold (> 256 to 64 µg/mL), whereas matched acidity decreased MICs 2-fold. In E. coli transformed with bla