Nanozymes modulate probiotic tryptophan metabolism to prevent Salmonella infection in mammalian models.

Probiotics are promising alternatives to antibiotics for the treatment of intestinal infections, but the effects of probiotics alone are often insufficient. Here we uncovered synergism between antibacterial iron-sulfur nanozymes (nFeS) and tryptophan derivatives that protects mice and pigs against bacterial gut infections. nFeS selectively inhibited potential intestinal pathogens while sparing commensal Lactobacillus vaginalis, whose presence enhanced the protective activity of nFeS against Salmonella enterica subsp. enterica serovar Typhimurium in vivo. Metabolomics and mutational analysis revealed that L. vaginalis synthesized 2-indolecarboxylic acid from a tryptophan derivative, indole-3-carboxaldehyde, a reaction that was catalysed by nFeS. The cytoplasmic pH of L. vaginalis (pH 7.5) allowed 2-indolecarboxylic acid to chelate free ferrous ions released by nFeS, thereby protecting it from antibacterial effects, whereas pathogens such as S. Typhimurium with a lower cytoplasmic pH were susceptible (pH 6.5). Pretreatment of pigs and mice with L. vaginalis and nFeS protected them against Salmonella infection. Our findings provide a foundation for improving probiotic bacteria-based therapies against intestinal infections.