A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus

Microbiol Spectr. 2023 Dec 12;11(6):e0159623. doi: 10.1128/spectrum.01596-23. Epub 2023 Oct 11.

Abstract

Biofilms are an important virulence factor in Staphylococcus aureus and are characterized by a structured microbial community consisting of bacterial cells and a secreted extracellular polymeric matrix. Inhibition of biofilm formation is an effective measure to control S. aureus infection. Here, we have synthesized a small molecule compound S-342-3, which exhibits potent inhibition of biofilm formation in both MRSA and MSSA. Further investigations revealed that S-342-3 exerts inhibitory effects on biofilm formation by reducing the production of polysaccharide intercellular adhesin and preventing bacterial adhesion. Our study has confirmed that the inhibitory effect of S-342-3 on biofilm is achieved by downregulating the expression of genes responsible for biofilm formation. In addition, S-342-3 is non-toxic to Galleria mellonella larvae and A549 cells. Consequently, this study demonstrates the efficacy of a biologically safe compound S-342-3 in inhibiting biofilm formation in S. aureus, thereby providing a promising antibiofilm agent for further research.

Keywords: PIA; Staphylococcus aureus; biofilm; cell adhesion; small-molecule.

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Adhesion
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biofilms
  • Humans
  • Methicillin-Resistant Staphylococcus aureus* / metabolism
  • Microbial Sensitivity Tests
  • Staphylococcal Infections* / drug therapy
  • Staphylococcal Infections* / microbiology
  • Staphylococcus aureus / genetics

Substances

  • Bacterial Proteins
  • Anti-Bacterial Agents