Can modified fragments of the human antimicrobial peptide LL-37 fight drug-resistant Candida fungal infections?

Five lipidated derivatives of KR12 (C10, C12, C14, 2-butyloctanoic acid, and 4-phenylbenzoic acid variants) showed strong antifungal activity against planktonic Candida cells, and C14-KR12-NH2 additionally disrupted Candida albicans biofilms—a notoriously drug-resistant state.

In vitro study synthesizing KR12-NH2 amide and 24 lipidated derivatives via fatty acid substitution; tested against Candida albicans, C. glabrata, C. tropicalis, and C. lipolytica; antifungal activity assessed for planktonic cells and biofilm cultures at 24/48/72 hours.

Candida infections kill hundreds of thousands of immunocompromised patients globally each year, and resistance to available antifungals is rising. Biofilm-forming Candida is particularly lethal and difficult to treat. A short, modifiable human-derived peptide fragment offers a novel, potentially resistance-resistant therapeutic approach.

This work is part of a broader effort to develop shorter, cheaper analogs of LL-37 that retain or enhance its antimicrobial properties. Lipidation is emerging as a general strategy for improving peptide potency and membrane disruption against both bacteria and fungi.

In vitro only—no animal model testing of antifungal efficacy or safety. Cytotoxicity to human cells was not fully characterized for all derivatives. Optimal lipid chain length may vary across Candida species. Biofilm results limited to C. albicans.