Mutations of the brpR and brpS genes affect biofilm formation in Staphylococcus aureus

BACKGROUND In the United States, Staphylococcus aureus(S. aureus) kills tens of thousands of individuals each year and the formation of a biofilm contributes to lethality.Biofilm-associated infections are hard to treat once the biofilm has formed. A new stilbene drug, labeled SK-03-92, was shown to kill S. aureus and affected transcription of two genes tied to a putative two-component system(TCS) we have named brpR(biofilm regulating protein regulator) and brpS(biofilm regulating protein sensor).AIM To determine if BrpR and BrpS regulate biofilm formation, brpR and brpS mutants were assessed using biofilm assays compared to wild-type S. aureus.METHODS A combination of biofilm and quantitative real-time-polymerase chain reaction assays were used. In addition, bioinformatic software tools were also utilized.RESULTS Significantly more biofilm was created in the brpR and brpS mutants vs wild-type cells. Quantitative real-time polymerase chain reactions showed the brpS mutant had differences in transcription of biofilm associated genes that were eight-fold higher for srtA, two-fold lower for lrgA, and 1.6-fold higher for cidA compared to wild-type. Bioinformatic analysis demonstrated that the S. aureus brpR/brpS TCS had homology to streptococcal late-stage competence proteins involved in celldeath, increased biofilm production, and the development of persister cells.CONCLUSION Our study suggests that brpR/brpS is a TCS that may repress S. aureus biofilm production and be linked to late-stage competence in S. aureus.