Antifungal effects of indolicidin-conjugated gold nanoparticles against fluconazole-resistant strains of Candida albicans isolated from patients with burn infection

Int J Nanomedicine. 2019 Jul 17:14:5323-5338. doi: 10.2147/IJN.S207527. eCollection 2019.

Abstract

Background: Candida albicans as an opportunistic fungus is one of the most important causes of late-onset morbidity and mortality in patients with major burns and severely impaired immune system. In recent years, the emergence of resistance to opportunistic fungi and toxicity of antimicrobial drugs make it necessary to develop new drugs. Methods: In the present study, we investigated anticandidal effects of indolicidin, as a representative of host defense peptide, conjugated with gold nanoparticles in fluconazole-resistant clinical isolates of C. albicans. After characterizing the conjugation of indolicidin using biophysical methodologies, the cytotoxicity and hemolytic activity of the nanocomplex were examined. In addition, the expression level of ERG11, responsible for antifungal resistance, and the immunomodulatory effect of peptide-nanomaterial conjugates were assessed. Results: Our data indicated that the nanocomplex was nontoxic for the fibroblast cells and erythrocytes. Treatment with the nanocomplex significantly reduced the expression levels of the ERG11 gene in fluconazole-resistant C. albicans isolates and the iNOS gene in macrophages. Conclusion: The study data provides a chance to develop innovative therapies for the treatment of C. albicans burn infections. However, further investigation is required to examine the efficiency of the nanocomplex.

Keywords: Candida albicans; antimicrobial peptides; burn infection; gold nanoparticles; indolicidin.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Burns / drug therapy
  • Burns / microbiology*
  • Candida albicans / drug effects*
  • Candida albicans / genetics
  • Candida albicans / isolation & purification*
  • Cell Death / drug effects
  • Drug Resistance, Fungal / drug effects
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Fluconazole / chemistry
  • Fluconazole / pharmacology*
  • Gene Expression Regulation, Fungal / drug effects
  • Genes, Fungal
  • Gold / pharmacology*
  • Hemolysis / drug effects
  • Humans
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • NIH 3T3 Cells
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism

Substances

  • Antifungal Agents
  • Antimicrobial Cationic Peptides
  • indolicidin
  • Gold
  • Fluconazole
  • Nitric Oxide Synthase Type II