| Membrane-targeted synergistic activity of docosahexaenoic acid and lysozyme against Pseudomonas aeruginosa. | |
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MedLine Citation:
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PMID: 19105793 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Antimicrobial polypeptides, including lysozymes, have membrane perturbing activity and are well-documented effector molecules of innate immunity. In cystic fibrosis, a hereditary disease with frequent lung infection with Pseudomonas aeruginosa, the non-esterified fatty acid DA (docosahexaenoic acid), but not OA (oleic acid), is decreased, and DA supplementation has been shown to improve the clinical condition in these patients. We hypothesized that DA may, either alone or in conjunction with lysozyme, exert antibacterial action against Ps. aeruginosa. We found that DA and lysozyme synergistically inhibit the metabolic activity of Ps. aeruginosa, in contrast with OA. Electron microscopy and equilibrium dialysis suggest that DA accumulates in the bacterial membrane in the presence of lysozyme. Surface plasmon resonance with live bacteria and differential scanning calorimetry studies with bacterial model membranes reveal that, initially, DA facilitates lysozyme incorporation into the membrane, which in turn allows influx of more DA, leading to bacterial cell death. The present study elucidates a molecular basis for the synergistic action of non-esterified fatty acids and antimicrobial polypeptides, which may be dysfunctional in cystic fibrosis. |
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Authors:
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Jose G Martinez; Michael Waldon; Qiyu Huang; Sandra Alvarez; Ami Oren; Natalie Sandoval; Ming Du; Feimeng Zhou; Alexandra Zenz; Karl Lohner; Robert Desharnais; Edith Porter |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: The Biochemical journal Volume: 419 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-10 Completed Date: 2009-03-24 Revised Date: 2011-08-05 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 193-200 Citation Subset: IM |
Affiliation:
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Department of Biological Sciences, California State University Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Calorimetry, Differential Scanning Cell Membrane / drug effects, metabolism Docosahexaenoic Acids / pharmacology* Drug Synergism Humans Microscopy, Electron, Transmission Muramidase / pharmacology* Pseudomonas aeruginosa / drug effects*, ultrastructure* Surface Plasmon Resonance |
| Grant Support | |
ID/Acronym/Agency:
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1P20 MD001824/MD/NCMHD NIH HHS; AI55675/AI/NIAID NIH HHS; GM61331/GM/NIGMS NIH HHS; P20 MD001824-010002/MD/NCMHD NIH HHS; P20 MD001824-020002/MD/NCMHD NIH HHS; P20 MD001824-030002/MD/NCMHD NIH HHS; P20 MD001824-040002/MD/NCMHD NIH HHS; R21 AI055675-01A1/AI/NIAID NIH HHS; R21 AI055675-02/AI/NIAID NIH HHS; R25 GM061331-09/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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25167-62-8/Docosahexaenoic Acids; EC 3.2.1.17/Muramidase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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