Antibacterial efficacy and mechanism of action of VTC3-knockout Saccharomyces cerevisiae against multidrug- resistant pathogenic bacteria

Abstract

Multidrug-resistant (MDR) bacterial infections are a global public health crisis, and traditional antibiotic therapies are becoming increasingly ineffective. Probiotics represent a promising strategy in this context. In this study, we examined the antibacterial activity and mechanism of action of Saccharomyces cerevisiae with VTC3 gene knockout ( VTC3- KO). Growth curves, biofilm formation, antibacterial spectrum, and coculture experiments demonstrated that VTC3- KO S. cerevisiae effectively inhibited the growth of pathogens and significantly suppressed the biofilm formation of Escherichia coli , Staphylococcus aureus , and Klebsiella pneumoniae . Moreover, VTC3- KO S. cerevisiae exhibited tolerance to the gastrointestinal environment, with enhanced auto and coaggregation with pathogens. In in vivo culture of Galleria mellonella and in a mouse infection model, VTC3- KO S. cerevisiae significantly improved host survival, alleviated intestinal tissue damage, and reduced inflammatory cell infiltration. Mechanistic studies suggest that the observed antimicrobial effect may be attributable to the production of acidic substances. These findings demonstrate that VTC3- KO S. cerevisiae possesses dual antibacterial and probiotic functions, providing a sustainable alternative to traditional antibiotics for treating MDR infections.