Document Detail


Membrane-targeted synergistic activity of docosahexaenoic acid and lysozyme against Pseudomonas aeruginosa.
MedLine Citation:
PMID:  19105793     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
3349633 - Analysis of the fatty acid composition of erythrocyte phospholipids by a base catalysed...
8166663 - Inhibition of diphosphatidylglycerol synthesis by u.v. a radiations in n.c.t.c. 2544 hu...
9600263 - Lovastatin and sodium phenylacetate normalize the levels of very long chain fatty acids...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Biochemical journal     Volume:  419     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-10     Completed Date:  2009-03-24     Revised Date:  2011-08-05    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  193-200     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, California State University Los Angeles, 5151 State University Drive, Los Angeles, CA 90032, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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:
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


Previous Document:  Peroxiredoxin 4 knockout results in elevated spermatogenic cell death via oxidative stress.
Next Document:  Demographics, guidelines, and clinical experience in severe community-acquired pneumonia.