MgrA Negatively Regulates Biofilm Formation and Detachment by Repressing the Expression of <i>psm</i> Operons in Staphylococcus aureus

Abstract

Phenol-soluble modulins (PSMs) are amphipathic peptides that are produced by staphylococci and play important roles in <i>Staphylococcus aureus</i> biofilm formation and dissemination. Although the multiple functions of PSMs have been recognized, the regulatory mechanisms controlling the expression of <i>psm</i> operons remain largely unknown. In this study, we identified MgrA in a DNA pulldown assay and further demonstrated, by electrophoretic mobility shift assays and DNase I footprinting assays, that MgrA could bind specifically to the promoter regions of <i>psm</i> operons. We then constructed an isogenic <i>mgrA</i> deletion strain and compared biofilm formation and detachment in the wild-type and isogenic <i>mgrA</i> deletion strains. Our results indicated that biofilm formation and detachment were significantly increased in the <i>mgrA</i> mutant strain. Real-time quantitative reverse transcription-PCR data indicated that MgrA repressed the transcription of <i>psm</i> operons in cultures and biofilms, suggesting that MgrA is a negative regulator of <i>psm</i> expression. Furthermore, we analyzed biofilm formation by the <i>psm</i> mutant strains, and we found that PSMs promoted biofilm structuring and development in the <i>mgrA</i> mutant strain. These findings reveal that MgrA negatively regulates biofilm formation and detachment by repressing the expression of <i>psm</i> operons through direct binding to the <i>psm</i> promoter regions.<b>IMPORTANCE</b><i>Staphylococcus aureus</i> is a human and animal pathogen that can cause biofilm-associated infections. PSMs have multiple functions in biofilm development and virulence in staphylococcal pathogenesis. This study has revealed that MgrA can negatively regulate <i>psm</i> expression by binding directly to the promoter regions of <i>psm</i> operons. Furthermore, our results show that MgrA can modulate biofilm structuring and development by repressing the production of PSMs in <i>S. aureus</i> Our findings provide novel insights into the regulatory mechanisms of <i>S. aureus psm</i> gene expression, biofilm development, and pathogenesis.