Cystathionine gamma-lyase (Staphylococcus aureus) (SaCSE)

Cystathionine gamma-lyase (SaCSE) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme in Staphylococcus aureus that plays a critical role in the bacterial sulfur metabolic pathway (UniProt P63890). It primarily catalyzes the conversion of cystathionine into cysteine, ammonia, and alpha-ketobutyrate, but it is also a major source of endogenous hydrogen sulfide (H2S) through the desulfhydration of cysteine (Shatalin et al., Science, 2011). In S. aureus, H2S acts as a potent antioxidant and signaling molecule that protects the pathogen from oxidative stress induced by the host immune system and bactericidal antibiotics (Mironov et al., Science, 2021). By sequestering reactive oxygen species and maintaining redox homeostasis, SaCSE contributes significantly to antibiotic tolerance and virulence. Consequently, SaCSE has emerged as a promising therapeutic target for the development of antibiotic potentiators. Small-molecule inhibitors of SaCSE, such as the compound NL1, have been shown to sensitize MRSA strains to conventional antibiotics, effectively reversing phenotypic resistance (Mironov et al., Science, 2021). Targeting this enzyme offers a strategy to enhance the efficacy of existing antimicrobial therapies while potentially slowing the emergence of further resistance.

Other names

CGLCSEL-cystathionine gamma-lyaseCystathionine gamma-lyase (S. aureus)

Inhibition of the enzyme's catalytic activity prevents the production of hydrogen sulfide (H2S), thereby compromising the bacterial defense against oxidative stress and potentiating the efficacy of bactericidal antibiotics.