Multifaceted Suppression of Staphylococcal Virulence Phenotypes: In Vitro Study of a Cellular Status With Reduced Agr Activity and Impaired Biofilm

Anti-quorum sensing (QS) therapy has been focused on to reduce the virulence of pathogenic bacteria. However, there is a risk that suppression of the staphylococcal QS Agr system might promote biofilm formation. In this study, we found that both Agr activity and the biofilm of Staphylococcus aureus can be reduced by a sappanwood extract (SWe). The impaired biofilm in the presence of SWe exhibited reduced extracellular DNA (eDNA) and increased extracellular polysaccharides. SWe also reduced pigmentation. The RNA-seq analysis showed that SWe suppressed multiple key virulence regulators, including the Agr and SaeRS systems. SWe downregulated cell-wall-associated proteins and several Agr-regulated virulence factors such as hemolysins and phenol-soluble modulins (PSMs). The present study did not intend the clinical application of the SWe but exemplified that it is possible to suppress multiple virulence phenotypes simultaneously in vitro, suggesting a new therapeutic concept to combat S. aureus infection.