Sulfhydryl compounds reduce Staphylococcus aureus biofilm formation by inhibiting PIA biosynthesis

Staphylococcus aureus is the most common opportunistic pathogen causing foreign-body-associated infections. It has been widely accepted that biofilms would help the bacteria to cope with variable environments. Here we showed that treatment with sulfhydryl compounds such as dithiothreitol, beta-mercaptoethanol or cysteine inhibited biofilm formation significantly in S. aureus. These sulfhydryl compounds at biofilm-inhibitive concentrations caused little inhibition of the growth rate and the initial adhesion ability of the cells. Real-time reverse transcriptase-PCR showed that the transcriptional level of ica, which encodes essential enzymes for polysaccharide intercellular adhesion (PIA) biosynthesis, was decreased after the treatment with thiols. Proteomic analysis revealed that Embden-Meyerhof-Parnas pathway and pentose phosphate pathway were strengthened while N-acetyl-glucosamine-associated polysaccharide metabolism was repressed in the cells treated with thiols. These changes finally resulted in the inhibition of PIA biosynthesis. We hope the discovery of this major physiological phenomenon will help in the prevention and clinical therapy of biofilm-associated problems caused by S. aureus.