Lasso peptide MccY alleviates non-typhoidal salmonellae-induced mouse gut inflammation via regulation of intestinal barrier function and gut microbiota

ABSTRACT Non-typhoidal salmonellae-induced zoonotic intestinal bleeding infections are a crucial threat to public health worldwide, and the development of new medications is required to prevent and treat non-typhoid Salmonella (NTS) infections. MccY, a class of lasso peptide, is effective in biological sterilization against Salmonella and Shigella. In this study, the therapeutic effect of MccY on S. Typhimurium-infected BALB/c mice has been discussed. specific pathogen free (SPF) mice were infected with the ST53 strain with bacterial loads of 106 and 103 CFU/mL, respectively, and then treated with 9.92 mg/kg BW MccY. Results revealed that MccY significantly reduced mouse mortality by 20%–40% and effectively alleviated weight loss and diarrhea. The integrity of the intestinal structure was protected, and the expression of TNF-α, IL-6, IL-10, and IL-18 was inhibited. Particularly, MccY exerted multiple effects on gut microbiota ecology, including direct elimination of Salmonella, showing promise in limiting infection to the gut level and thereby halting the transmission of NTS. MccY indirectly inhibited other opportunistic pathogens and partially restored the microbiota, promoting an increase in Bacteroidetes, Lactobacillus, Muribaculum, and Clostridium. Consequently, this work provides an understanding of the link between host infection and therapeutic application of MccY. IMPORTANCE Diseases caused by Enterobacteriaceae multidrug-resistant strains have become increasingly difficult to manage. It is necessary to verify the new antibacterial drug MccY effect on non-typhoid Salmonella infection in mice since it is regarded as a promising microcin. The results demonstrated that MccY has a potential therapeutic application value in the protection against Salmonella-induced intestinal damage and alleviating related intestinal dysbiosis and metabolic disorders. MccY could be a promising candidate as an antimicrobial or anti-inflammatory agent for treating infectious diseases.