Isovitexin, a Potential Candidate Inhibitor of Sortase A of Staphylococcus aureus USA300

J Microbiol Biotechnol. 2018 Sep 28;28(9):1426-1432. doi: 10.4014/jmb.1802.02014.

Abstract

Staphylococcus aureus (S. aureus) causes a broad variety of diseases. The spread of multidrugresistant S. aureus highlights the need to develop new ways to combat S. aureus infections. Sortase A (SrtA) can anchor proteins containing LPXTG binding motifs to the bacteria surface and plays a key role in S. aureus infections, making it a promising antivirulence target. In the present study, we used aSrtA activity inhibition assay to discover that isovitexin, a Chinese herbal product, can inhibit SrtA activity with an IC50 of 28.98 μg/ml. Using a fibrinogenbinding assay and a biofilm formation assay, we indirectly proved the SrtA inhibitory activity of isovitexin. Additionally, isovitexin treatment decreased the amount of staphylococcal protein A (SpA) on the surface of the cells. These data suggest that isovitexin has the potential to be an anti-infective drug against S. aureus via the inhibition of sortase activity.

Keywords: Staphylococcus aureu; antivirulence; inhibitor; isovitexin; sortase A.

MeSH terms

  • Aminoacyltransferases / antagonists & inhibitors*
  • Aminoacyltransferases / genetics
  • Aminoacyltransferases / isolation & purification
  • Aminoacyltransferases / metabolism
  • Anti-Infective Agents / pharmacology*
  • Apigenin / pharmacology*
  • Bacterial Adhesion / drug effects
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / metabolism
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / isolation & purification
  • Cysteine Endopeptidases / metabolism
  • Drugs, Chinese Herbal / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / pathogenicity
  • Staphylococcus aureus / physiology*
  • Virulence Factors / metabolism

Substances

  • Anti-Infective Agents
  • Bacterial Proteins
  • Drugs, Chinese Herbal
  • Enzyme Inhibitors
  • Virulence Factors
  • Apigenin
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases
  • isovitexin