Sortase A-Inhibitory Metabolites from a Marine-Derived Fungus Aspergillus sp

Mar Drugs. 2020 Jul 13;18(7):359. doi: 10.3390/md18070359.

Abstract

Seven alkaloidal compounds (2-8) and one polyketide (1) were isolated from a semisolid rice culture of the marine-derived fungus Aspergillus sp. F452. Structures of the isolated compounds were elucidated based on spectroscopic data and comparisons with previously reported data. The alkaloidal compounds (2-8) displayed weak to moderate inhibitory activities against Staphylococcus aureus-derived sortase A (SrtA) without affecting cell viability. Aspermytin A (1) strongly inhibited SrtA activity, with an IC50 value of 146.0 μM, and significantly reduced bacterial adherence to fibronectin-coated surfaces. The present results indicate that the underlying mechanism of action of compound 1 is associated with the inhibition of SrtA-mediated S. aureus adhesion to fibronectin, thus potentially serving as an SrtA inhibitor.

Keywords: Aspergillus sp.; fibronectin; marine-derived fungus; metabolites; sortase A.

Publication types

  • Comparative Study

MeSH terms

  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology*
  • Aminoacyltransferases / antagonists & inhibitors*
  • Aminoacyltransferases / metabolism
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Aspergillus / metabolism*
  • Bacterial Adhesion / drug effects
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Cell Line, Tumor
  • Cysteine Endopeptidases / metabolism
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Fibronectins / metabolism
  • Humans
  • Kinetics
  • Molecular Structure
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / enzymology
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Fibronectins
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases