Dermatophytic defensin with antiinfective potential

Zhu, Shunyi, Gao, Bin, Harvey, Peta J. and Craik, David J. (2012) Dermatophytic defensin with antiinfective potential. Proceedings of the National Academy of Sciences of the United States of America, 109 22: 8495-8500. doi:10.1073/pnas.1201263109


Author Zhu, Shunyi
Gao, Bin
Harvey, Peta J.
Craik, David J.
Total Author Count Override 4
Title Dermatophytic defensin with antiinfective potential
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2012-05-01
Sub-type Article (original research)
DOI 10.1073/pnas.1201263109
Open Access Status Not Open Access
Volume 109
Issue 22
Start page 8495
End page 8500
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Collection year 2013
Language eng
Abstract 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 α-helical and β-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 froma large resource of fungal genomes.
Keyword Ascomycota
Methicillin-resistant Staphylococcus aureus
Plectasin
Mouse peritonitis model
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print 14 May 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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