In situ anchoring of biocompatible ergothioneine-gold nanoantibiotic on Spirulina for oral therapy of bacterial enteritis.

Severe bacterial enteritis causes significant clinical manifestations and has a widespread impact, while conventional antibiotic treatments have exacerbated antimicrobial resistance, underscoring the urgent need for effective therapeutic alternatives. To address this critical gap, we develop a biohybrid therapeutic platform that combines antibacterial ergothioneine-capped gold nanoclusters (EGT-Au NCs) with Spirulina for oral delivery. EGT alone has no antibacterial activity, yet the engineered EGT-Au NCs exhibit antibacterial efficacy approaching that of conventional antibiotics, while also minimizing the risk of resistance. Beyond their potent antibacterial activity, EGT-Au NCs display exceptional biocompatibility, negligible hemolytic toxicity, enhanced anti-inflammatory and antioxidant properties that collectively promote host recovery. By harnessing the natural gastrointestinal adhesion and prolonged retention of Spirulina (EGT-Au NCs@SP), this system enhances localized antimicrobial efficacy. In vivo studies confirm the EGT-Au NCs@SP platform exhibits robust antibacterial performance, effective inflammation suppression, and enhanced intestinal repair in Salmonella Typhimurium infection models. Mechanistic investigations demonstrate that EGT-Au NCs exert a sophisticated antibacterial mechanism, actively disarming bacteria by impairing flagellar assembly, disrupting biofilm formation, attenuating bacterial virulence, and significantly reducing epithelial invasion. Notably, Salmonella Typhimurium strains that acquired resistance to conventional antibiotics remainsensitive to EGT-Au NCs. This multifunctional biohybrid nanoplatform represents a safe and effective oral therapeutic strategy, offering a promising alternative to antibiotics for combating gastrointestinal infections and antimicrobial resistance.