Synergy of histone acetyltransferase inhibitor (HATi) with quercetin inhibits biofilm formation in Candida tropicalis

Lett Appl Microbiol. 2024 Sep 2;77(9):ovae085. doi: 10.1093/lambio/ovae085.

Abstract

Histone acetyltransferase inhibitors (HATi) are mechanism-based inhibitors that show promise in the treatment of several illnesses, including diabetes, hyperlipidemia, cancer, and Alzheimer's disease. The work emphasizes the significance of HATi as a possible treatment strategy against Candida species biofilms. Here, in this study, we found that combining a HATi, anacardic acid (AA), and quercetin, a known flavonoid, significantly prevented biofilm formation by C. tropicalis. We further show that C. tropicalis exhibited a considerable downregulation of drug-resistance gene expression (CDR1 and MDR1) when co-administrated. Additionally, in silico studies revealed that the AA interacts strongly with a histone acetyltransferase, Rtt109, which may account for the observed biofilm inhibitory effect. In conclusion, the study illustrates how HATi may be used to potentiate the inhibitory action of phytoactives or antifungals against drug-resistant yeast infections.

Keywords: CDR1; HAT; HATi; MDR1; biofilm; quercetin; synergy.

MeSH terms

  • Anacardic Acids* / pharmacology
  • Antifungal Agents* / pharmacology
  • Biofilms* / drug effects
  • Candida tropicalis* / drug effects
  • Drug Resistance, Fungal
  • Drug Synergism*
  • Enzyme Inhibitors / pharmacology
  • Fungal Proteins / antagonists & inhibitors
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Histone Acetyltransferases* / antagonists & inhibitors
  • Histone Acetyltransferases* / genetics
  • Histone Acetyltransferases* / metabolism
  • Microbial Sensitivity Tests
  • Quercetin* / pharmacology

Substances

  • Quercetin
  • Antifungal Agents
  • Histone Acetyltransferases
  • Anacardic Acids
  • anacardic acid
  • Enzyme Inhibitors
  • Fungal Proteins

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