The Catestatin-Derived Peptides Are New Actors to Fight the Development of Oral Candidosis

Int J Mol Sci. 2022 Feb 13;23(4):2066. doi: 10.3390/ijms23042066.

Abstract

Resistance to antifungal therapy of Candida albicans and non-albicans Candida strains, frequently associated with oral candidosis, is on the rise. In this context, host-defense peptides have emerged as new promising candidates to overcome antifungal resistance. Thus, the aim of this study was to assess the effectiveness against Candida species of different Catestatin-derived peptides, as well as the combined effect with serum albumin. Among Catestatin-derived peptides, the most active against sensitive and resistant strains of C. albicans, C. tropicalis and C. glabrata was the D-isomer of Cateslytin (D-bCtl) whereas the efficiency of the L-isomer (L-bCtl) significantly decreases against C. glabrata strains. Images obtained by transmission electron microscopy clearly demonstrated fungal membrane lysis and the leakage of the intracellular material induced by the L-bCtl and D-bCtl peptides. The possible synergistic effect of albumin on Catestatin-derived peptides activity was investigated too. Our finding showed that bovine serum albumin (BSA) when combined with the L- isomer of Catestatin (L-bCts) had a synergistic effect against Candida albicans especially at low concentrations of BSA; however, no synergistic effect was detected when BSA interacted with L-bCtl, suggesting the importance of the C-terminal end of L-bCts (GPGLQL) for the interaction with BSA. In this context in vitro D-bCtl, as well as the combination of BSA with L-bCts are potential candidates for the development of new antifungal drugs for the treatment of oral candidosis due to Candida and non-Candida albicans, without detrimental side effects.

Keywords: Catestatin; antifungal; antimicrobial peptides; candidosis; resistance.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology
  • Candida / drug effects
  • Candida / metabolism
  • Candidiasis, Oral / drug therapy*
  • Candidiasis, Oral / metabolism
  • Cattle
  • Chromogranin A / pharmacology*
  • Drug Resistance, Fungal / drug effects
  • Humans
  • Peptide Fragments / pharmacology*
  • Peptides / pharmacology*
  • Serum Albumin, Bovine / metabolism

Substances

  • Antifungal Agents
  • Chromogranin A
  • Peptide Fragments
  • Peptides
  • chromogranin A (344-364)
  • Serum Albumin, Bovine