Tea polyphenols amplify oxidative stress-induced eradication of Staphylococcus aureus by disrupting the hydrogen sulfide (H2S) signaling pathway.

Endogenous hydrogen sulfide (H2S) acts as a pivotal shield for Staphylococcus aureus against oxidative stress. Although tea polyphenols (TPs) are established antibacterial agents, their precise mechanistic impact on H2S-linked redox regulation has yet to be fully elucidated. Here, we test the hypothesis that TPs exert their bactericidal effect on S. aureus by compromising its intrinsic H2S-mediated antioxidant defense system. DL-Propargylglycine (PAG) was used to construct an H2S synthesis-inhibited model (designated WT + inh). The response of this model to TPs was evaluated against that of the wild-type (WT) strain by growth curve analysis, flow cytometry analysis, and scanning electron microscopy (SEM). In addition, reactive oxygen species (ROS), antioxidant enzyme activities, including superoxide dismutase (SOD) and catalase (CAT), the oxidative damage marker malondialdehyde (MDA), and the expression of oxidative stress- and sulfur metabolism-related genes were determined. Finally, exogenous H2S supplementation was used to examine whether sulfide could modify the response to TPs. PAG treatment significantly enhanced bacterial susceptibility to TPs, concomitant with increased cell death and exacerbated morphological damage. Intracellular activities of SOD and CAT were reduced, whereas ROS and MDA levels were significantly elevated. Exogenous H2S modulated the growth inhibitory effects of TPs. The TP-associated oxidative damage coincided with changes in H2S-related sulfur metabolism and antioxidant gene expression. These findings support an association between H2S-related antioxidant defense and the susceptibility of S. aureus to TPs, providing a basis for further investigation of H2S metabolism in tea polyphenol-based antibacterial strategies.