CLEC3A-derived peptides exhibit broad-spectrum activity against Candida auris and clinically relevant pathogens

Katinka Mies1, Gabriele Hermes1, Jens Beckers1

  • 1Institute for Clinical Chemistry, Medical Faculty, University of Cologne, Cologne, Germany.

Abstract

Insights

Two novel antimicrobial peptides, HT-47 and WRK-30, show potent broad-spectrum activity against drug-resistant bacteria and fungi, including the critical pathogen Candida auris. These peptides effectively combat infections by damaging microbial membranes, offering new therapeutic potential.

Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • Antimicrobial resistance (AMR) is a global health crisis, with Candida auris identified as a critical priority pathogen by the WHO.
  • Antimicrobial peptides (AMPs) are a promising therapeutic avenue due to their broad-spectrum activity and membrane-disruptive mechanisms.

Purpose of the Study:

  • To evaluate the antibacterial and antifungal efficacy of two CLEC3A-derived peptides, HT-47 and WRK-30.
  • To compare their activity against reference AMP LL-37 and existing antifungal/antibiotic drugs.

Main Methods:

  • Viable count assays were used to determine minimum inhibitory concentrations (MIC50).
  • Biofilm inhibition assays assessed anti-biofilm potential.
  • Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) visualized cellular damage.

Main Results:

  • HT-47 and WRK-30 demonstrated significant antibacterial activity against ESKAPE pathogens (K. pneumoniae, A. baumannii).
  • Both peptides exhibited potent antifungal activity against C. albicans, C. neoformans, and notably C. auris, with MIC50 values comparable or superior to amphotericin B.
  • Significant inhibition of C. auris biofilm formation was observed, alongside extensive membrane and subcellular damage in treated fungal cells.

Conclusions:

  • CLEC3A-derived peptides HT-47 and WRK-30 possess potent antibacterial and antifungal properties.
  • These peptides show significant potential as therapeutic agents against multidrug-resistant pathogens, including Candida auris.