Combined antibiofilm activity of synthetic peptides and antifungal drugs against Candida spp

Future Microbiol. 2022 Sep:17:1133-1146. doi: 10.2217/fmb-2022-0053. Epub 2022 Jul 26.

Abstract

Introduction: Candida krusei and Candida albicans are biofilm-forming drug-resistant yeasts that cause bloodstream infections that can lead to death. Materials & methods: nystatin and itraconazole were combined with two synthetic peptides, PepGAT and PepKAA, to evaluate the synergistic effect against Candida biofilms. Additionally, scanning electron and fluorescence microscopies were employed to understand the mechanism behind the synergistic activity. Results: Peptides enhanced the action of drugs to inhibit the biofilm formation of C. krusei and C. albicans and the degradation of mature biofilms of C. krusei. In combination with antifungal drugs, peptides' mechanism of action involved cell wall and membrane damage and overproduction of reactive oxygen species. Additionally, in combination, the peptides reduced the toxicity of drugs to red blood cells. Conclusion: These results reveal that the synthetic peptides enhanced the antibiofilm activity of drugs, in addition to reducing their toxicity. Thus, these peptides have strong potential as adjuvants and to decrease the toxicity of drugs.

Keywords: Candida; action mechanisms; antibiofilm activity; antifungal drugs; candidiasis; clinical application; nystatin and itraconazole; synergism; synthetic peptides.

Plain language summary

Candida krusei and Candida albicans are biofilm-forming, drug-resistant yeasts that cause bloodstream infections that can lead to death. In this study, biofilms of C. krusei and C. albicans were treated with a solution composed of synthetic peptides and antifungal drugs, none of which were effective alone. The synthetic peptides reduced the toxicity of drugs to red blood cells. These results may pave the way to the application of synthetic peptides as a beneficial additional to antifungal drugs to treat fungi that cannot be killed by drugs alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents* / pharmacology
  • Antifungal Agents* / therapeutic use
  • Biofilms
  • Candida albicans
  • Candida*
  • Microbial Sensitivity Tests
  • Peptides / pharmacology

Substances

  • Antifungal Agents
  • Peptides