SpoVG Modulates Cell Aggregation in Staphylococcus aureus by Regulating sasC Expression and Extracellular DNA Release

Biofilm formation is involved in numerous Staphylococcus aureus infections such as endocarditis, septic arthritis, osteomyelitis, and infections of indwelling medical devices. In these diseases, S. aureus forms biofilms as cell aggregates interspersed in host matrix material. Here, we have observed that the level of cell aggregation was significantly higher in the isogenic spoVG-deletion strain than in the wild-type strain. Reverse transcription-quantitative PCR data indicated that SpoVG could repress the expression of sasC, which codes for S. aureus surface protein C and is involved in cell aggregation and biofilm accumulation. Electromagnetic mobility shift assay demonstrated that SpoVG could specifically bind to the promoter region of sasC, indicating that SpoVG is a negative regulator and directly represses the expression of sasC. In addition, deletion of the SasC aggregation domain in the spoVG-deletion strain indicated that high-level expression of sasC could be the underlying cause of significantly increased cell aggregation formation. Our previous study showed that SpoVG is involved in oxacillin resistance of methicillin-resistant S. aureus by regulating the expression of genes involved in cell wall synthesis and degradation. In this study, we also found that SpoVG was able to negatively modulate the S. aureus drug tolerance under conditions of a high concentration of oxacillin treatment. These findings can broaden our understanding of the regulation of biofilm formation and drug tolerance in S. aureus. IMPORTANCE This study revealed that SpoVG can modulate cell aggregation by repressing sasC expression and extracellular DNA (eDNA) release. Furthermore, we have demonstrated the potential linkage between cell aggregation and antibiotic resistance. Our findings provide novel insights into the regulatory mechanisms of SpoVG involved in cell aggregation and in biofilm development and formation in Staphylococcus aureus.