Arginine Reprograms Host Metabolism and Bacterial Membrane Integrity to Resensitize MRSA to Oxacillin sodium

While combining metabolites with antibiotics represents a promising approach to combat multidrug-resistant bacteria, the mechanisms underlying metabolite-mediated antibiotic enhancement remain poorly understood. Here, we report that exogenous arginine (Arg) significantly enhances the antibacterial activity of oxacillin sodium (OXA) against MRSA both in vitro and in vivo.

The combination of Arg and OXA can reduce the survival rate of USA300 by 4 log units in vitro, and can also reduce the bacterial load in organs and alleviate the pathological damage to the kidneys and liver in vivo. Mechanistically, Arg disrupts bacterial membrane integrity and increases intracellular accumulation of OXA. Furthermore, Arg promotes macrophage polarization and mitigates host cell pyroptosis induced by USA300, thereby alleviating inflammatory infection and improving host survival.