Targeting adhesion in fungal pathogen Candida albicans

Future Med Chem. 2021 Feb;13(3):313-334. doi: 10.4155/fmc-2020-0052. Epub 2020 Jun 22.

Abstract

Fungal infections with increasing resistance to conventional therapies are a growing concern. Candida albicans is a major opportunistic yeast responsible for mucosal and invasive infections. Targeting the initial step of the infection process (i.e., C. albicans adhesion to the host cell) is a promising strategy. A wide variety of molecules can interfere with adhesion processes via an assortment of mechanisms. Herein, we focus on how small molecules disrupt biosynthesis of fungal cell wall components and membrane structure, prevent the localization of GPI-anchor proteins, inhibit production of enzymes involved in adhesion, downregulate genes encoding adhesins and competitively inhibit receptor interactions. As a result, adhesion of C. albicans to host cells is reduced, paving the way to new classes of antifungal agents.

Keywords: Candida albicans; adhesion inhibitors; anti-adhesion therapies; antifungal agents; antimicrobial resistance; virulence factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antifungal Agents / chemistry*
  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology
  • Aspartic Acid Proteases / antagonists & inhibitors
  • Aspartic Acid Proteases / metabolism
  • Candida albicans / metabolism*
  • Candida albicans / pathogenicity
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Wall / drug effects
  • Cell Wall / metabolism
  • Fungal Proteins / antagonists & inhibitors
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / metabolism
  • Polyphenols / chemistry
  • Polyphenols / metabolism
  • Polyphenols / pharmacology
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / metabolism
  • Quaternary Ammonium Compounds / pharmacology
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / metabolism
  • Small Molecule Libraries / pharmacology

Substances

  • ALA1 protein, Candida albicans
  • Antifungal Agents
  • Cell Adhesion Molecules
  • Fungal Proteins
  • GPI-Linked Proteins
  • Polyphenols
  • Quaternary Ammonium Compounds
  • Small Molecule Libraries
  • Aspartic Acid Proteases