Bacterial cystathionine γ-lyase (bCSE)

Bacterial cystathionine γ-lyase (bCSE) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that plays a critical role in bacterial sulfur metabolism and the production of hydrogen sulfide (H2S) [1, 11]. In major human pathogens like Staphylococcus aureus and Pseudomonas aeruginosa, bCSE is the primary generator of H2S, which serves as a potent antioxidant and signaling molecule [1, 4]. This endogenous H2S protects bacteria from oxidative stress induced by the host immune system and bactericidal antibiotics, thereby contributing to antibiotic resistance and the formation of persister cells [3, 5]. Targeting bCSE with small-molecule inhibitors, such as 6-bromoindole derivatives (e.g., NL1, MNS1), has emerged as a promising strategy to sensitize drug-resistant bacteria to existing antibiotics [1, 6, 7]. By blocking H2S production, these inhibitors disrupt the bacterial defense system, suppress biofilm formation, and enhance the efficacy of antibiotics like gentamicin and ampicillin [2, 4]. A key challenge in drug development is achieving high selectivity for the bacterial enzyme over the human ortholog (hCSE) to minimize potential toxicity related to human H2S signaling [6, 13].

Other names

Cystathionine gamma-lyaseCGLCSECystathionaseMccBYhrBCseL-cystathionine cysteine-lyase (deaminating)

Inhibition of bacterial hydrogen sulfide production to potentiate bactericidal antibiotics and disrupt bacterial defense mechanisms.