2lr5

Publication Abstract from PubMed

Fungi are a newly emerging source of peptide antibiotics with therapeutic potential. Here, we report 17 new fungal defensin-like peptide (fDLP) genes and the detailed characterization of a corresponding synthetic fDLP (micasin) from a dermatophyte in terms of its structure, activity and therapeutic potential. NMR analysis showed that synthetic micasin adopts a "hallmark" cysteine-stablized alpha-helical and beta-sheet fold. It was active on both Gram-positive and Gram-negtive bacteria, and importantly it killed two clinical isolates of methicillin-resistant Staphylococcus aureus and the opportunistic pathogen Pseudomonas aeruginosa at low micromolar concentrations. Micasin killed approximately 100% of treated bacteria within 3 h through a membrane nondisruptive mechanism of action, and showed extremely low hemolysis and high serum stability. Consistent with these functional properties, micasin increases survival in mice infected by the pathogenic bacteria in a peritonitis model. Our work represents a valuable approach to explore novel peptide antibiotics from a large resource of fungal genomes.

Dermatophytic defensin with antiinfective potential.,Zhu S, Gao B, Harvey PJ, Craik DJ Proc Natl Acad Sci U S A. 2012 May 29;109(22):8495-500. Epub 2012 May 14. PMID:22586077^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.