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Small-Molecule Morphogenesis Modulators Enhance the Ability of 14-Helical β-Peptides To Prevent Candida albicans

Angélica de L Rodríguez López1, Myung-Ryul Lee2, Nathan B Wang2

  • 1Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Antimicrobial Agents and Chemotherapy
|June 19, 2019
PubMed

Insights

New antifungal β-peptides show promise in preventing drug-resistant Candida albicans biofilms. Combining these peptides with isoamyl alcohol significantly enhances efficacy and reduces treatment toxicity.

Area of Science:

  • Mycology
  • Biochemistry
  • Antimicrobial drug development

Background:

  • Candida albicans causes serious infections, often forming drug-resistant biofilms.
  • Rising antifungal resistance necessitates novel strategies for biofilm control.
  • Antimicrobial peptides (AMPs) are a potential source for new antifungal agents.

Purpose of the Study:

  • To investigate the efficacy of novel 14-helical β-peptides against Candida albicans biofilms.
  • To evaluate the synergistic potential of combining β-peptides with morphogenesis modulators like isoamyl alcohol.
  • To assess the safety profile of these combination therapies.

Main Methods:

  • Design and synthesis of 14-helical β-peptides mimicking natural AMPs.
  • In vitro and in vivo testing of β-peptides for antifungal and antibiofilm activity.
  • Combination studies with morphogenesis modulators (1-dodecanol, isoamyl alcohol, farnesol) to determine Minimum Biofilm Prevention Concentrations (MBPCs).
  • Hemolysis assays to evaluate compound toxicity.

Main Results:

  • Amphiphilic, cationic β-peptides demonstrated antifungal activity and inhibited biofilm formation.
  • Isoamyl alcohol significantly reduced the MBPCs of β-peptides by up to 128-fold.
  • Combination therapies showed minimal hemolysis (<10%) at effective concentrations.

Conclusions:

  • Combination therapy of morphogenesis modulators and antifungal β-peptides offers a promising strategy for preventing Candida albicans biofilms.
  • This approach may overcome current antifungal resistance challenges.
  • Further development of these combination therapies could lead to improved treatments for candidiasis.
Keywords:
Candida albicansantimicrobial peptide mimeticbiofilmmorphogenesis

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