Dermatophytic defensin with antiinfective potential.

Proceedings of the National Academy of Sciences of the United States of America
Shunyi ZhuDavid J Craik

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-stabilized α-helical and β-sheet fold. It was active on both gram-positive and gram-negative 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.

References

Feb 1, 1996·Protein Science : a Publication of the Protein Society·E G Hutchinson, J M Thornton
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Jan 25, 2002·Nature·Michael Zasloff
Nov 5, 2002·Nature Reviews. Drug Discovery·Anthony CoatesClive Page
Feb 11, 2005·Nature Reviews. Microbiology·Kim A Brogden
Jun 17, 2006·Nature Reviews. Microbiology·Andreas Peschel, Hans-Georg Sahl
Aug 8, 2006·Current Opinion in Pharmacology·Alexandra K MarrRobert Ew Hancock
Dec 13, 2006·Nature Biotechnology·Robert E W Hancock, Hans-Georg Sahl
Aug 19, 2007·Nature Reviews. Microbiology·Michael R Yeaman, Nannette Y Yount
Nov 28, 2007·Expert Review of Anti-infective Therapy·John D F Hale, Robert E W Hancock
Feb 16, 2008·The British Journal of Dermatology·A L CogenR L Gallo
Aug 5, 2008·Biochemical and Biophysical Research Communications·Shintaro HaraShigeru Kohno
Dec 18, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bin GaoShunyi Zhu
Aug 18, 2009·Trends in Biotechnology·Donna M EastonRobert E W Hancock
Sep 8, 2009·Current Opinion in Pharmacology·Martti Vaara
Feb 20, 2010·Science·Nityakalyani SrinivasJohn A Robinson
May 29, 2010·Science·Tanja SchneiderHans-Henrik Kristensen
Sep 24, 2010·The Journal of Biological Chemistry·Nicole L van der WeerdenMarilyn A Anderson
Feb 18, 2011·British Journal of Pharmacology·Anthony R M CoatesYanmin Hu
May 5, 2011·Developmental and Comparative Immunology·Yanbing Wang, Shunyi Zhu
Jul 19, 2011·Biochemical and Biophysical Research Communications·Bin GaoShunyi Zhu

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Citations

Oct 25, 2012·The Journal of Biological Chemistry·Jesper S OeemigReinhard Wimmer
Nov 16, 2013·ACS Chemical Biology·Bin Gao, Shunyi Zhu
Jan 16, 2014·Molecular Biology and Evolution·Shunyi ZhuJan Tytgat
Sep 19, 2014·Pharmaceuticals·Jiajia WuShunyi Zhu
Oct 30, 2012·Biochemical and Biophysical Research Communications·Kuanyu ZhuShunyi Zhu
Sep 15, 2012·Biochemical and Biophysical Research Communications·Bin Gao, Shunyi Zhu
Sep 12, 2015·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Xueli WangShunyi Zhu
Aug 26, 2016·Cellular and Molecular Life Sciences : CMLS·Thomas M A ShafeeMark D Hulett
Sep 28, 2016·Protein Engineering, Design & Selection : PEDS·Shangfei ZhangShunyi Zhu
May 9, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Markus Künzler
Feb 23, 2018·FEMS Microbiology Reviews·Aurélie DeveauLukas Y Wick
Apr 27, 2019·Applied Microbiology and Biotechnology·Na YangJianhua Wang
Jan 29, 2016·The Journal of Biological Chemistry·Lanxia MengYingliang Wu
Apr 17, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiajia WuShunyi Zhu
Oct 25, 2014·The Journal of Biological Chemistry·Andreas EssigMarkus Aebi
Sep 13, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bingzheng ShenYan Yu
Dec 18, 2020·Cellular Microbiology·Michaela DümigSven Krappmann
Dec 12, 2020·Journal of Pharmaceutical and Biomedical Analysis·Rekha Mol Kollakalnaduvil RaghavanElyas Kk
Nov 21, 2019·Developmental and Comparative Immunology·Gabriela ContrerasMichael Wink
Aug 26, 2019·Ticks and Tick-borne Diseases·Alejandro Cabezas-CruzManuel Rodriguez-Valle
Aug 7, 2021·Journal of Fungi·Bin Gao, Shunyi Zhu
Aug 22, 2017·Biochemistry·Marco FranzoiAndreas Essig

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