2026-10-12T14:59:42Z https://www.scidb.cn/oai

10.57760/sciencedb.010ux 2026-08-31T10:11:40Z

2026-08-31 Arginine Reprograms Host Metabolism and Bacterial Membrane Integrity to Resensitize MRSA to Oxacillin sodium doi:10.57760/sciencedb.010ux en The urgent need for therapeutic strategies against methicillin-resistant Staphylococcus aureus (MRSA) drives the search for novel antibacterial agents or adjuvants. 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. Thus, our study reveals that arginine acts as a dual-targeting metabolic adjuvant that not only potentiates oxacillin activity but also modulates host immune responses, offering a promising therapeutic strategy for treating MRSA infections. Antibiotic adjuvant; bacterial resistance; arginine; macrophage; pyroptosis Dong Chunliu PUBLIC https://creativecommons.org/licenses/by-nc-nd/4.0/ dataset Science Data Bank