Inhibitory Effect of Staphylococcus Epidermidis Fermentation Broth on Staphylococcus Aureus

In this study, Staphylococcus epidermidis (S. epidermidis) fermentation broth with an inhibitory effect on Staphylococcus aureus (S. aureus) was produced by optimizing cultivation conditions. S. epidermidis fermentation broth cultivated in NA medium (SFB) does not inhibit the growth of S. aureus, whereas Gly-SFB or Glu-SFB, prepared by incorporating glycerol or glucose into NA medium, significantly inhibited S. aureus growth. GC‒MS and HPLC revealed several fatty acids in Gly-SFB and Glu-SFB, which inhibited the growth of S. aureus. LC‒MS/MS combined with untargeted metabolomics was used to examine the differentially abundant metabolites in the fermentation broth. The results revealed that the main differentially abundant metabolites of the fermentation broths were carboxylic acids and their derivatives, which included peptides containing lysine, arginine, and hydrophobic amino acid residues, which may be the principal compounds that inhibit the growth of S. aureus in the fermentation broth. Scanning Electron Microscope (SEM) and Propidium iodide (PI) staining results indicated that the cell membrane of S. aureus was compromised following treatment with Gly-SFB or Glu-SFB, significantly increasing the extracellular ATP levels of S. aureus. The dependence on carbon sources altered the metabolic pathway of S. epidermidis, resulting in the growth suppression of S. aureus by Gly-SFB and Glu-SFB. The inhibitory effect mostly relies on the presence of fatty acids in the fermentation broth and the synergistic interactions among other compounds.