Acid-Mediated Antimicrobial Activity and Probiotic Potential of an SKS1-knockout Saccharomyces Cerevisiae Strain

Bacterial infections pose a significant threat to human health, and the prudent use of antibiotics remains a critical component of disease treatment and control. The increase in drug resistance of pathogenic bacteria poses a huge challenge to the world. Probiotics have become a promising approach to combating pathogenic bacterial infections. In this research, we found that the SKS1-KO Saccharomyces cerevisiae showed effective antibacterial activity against common clinical pathogenic bacteria in vitro, which has been confirmed through the determination of the minimum inhibitory concentration (MIC), growth curve analysis, inhibitory spectrum analysis and co-culture experiments. This strain has remarkable self-aggregation and co-aggregation characteristics. In addition, we used Galleria mellonella infected with Escherichia coli and Staphylococcus aureus as a model to evaluate the antibacterial activity of the SKS1-KO strain in vivo. We found that treatment with this strain significantly prolonged the survival time of the G. mellonella. Mass spectrometric quantification revealed significantly elevated levels of acetic acid, propionic acid, isobutyric acid, isovaleric acid, and hexanoic acid in the SKS1-KO cell-free supernatant (CFS) compared with the parental BY4743 strain. Exogenous supplementation of these fatty acids to BY4743 CFS enhanced its antibacterial activity, confirming that the increased accumulation of multiple fatty acids contributes to the enhanced phenotype. The SKS1-KO strain shows potential as a probiotic candidate for further preclinical development.