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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5968
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pubmed:dateCreated |
2010-2-19
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pubmed:abstractText |
Antibiotics with new mechanisms of action are urgently required to combat the growing health threat posed by resistant pathogenic microorganisms. We synthesized a family of peptidomimetic antibiotics based on the antimicrobial peptide protegrin I. Several rounds of optimization gave a lead compound that was active in the nanomolar range against Gram-negative Pseudomonas spp., but was largely inactive against other Gram-negative and Gram-positive bacteria. Biochemical and genetic studies showed that the peptidomimetics had a non-membrane-lytic mechanism of action and identified a homolog of the beta-barrel protein LptD (Imp/OstA), which functions in outer-membrane biogenesis, as a cellular target. The peptidomimetic showed potent antimicrobial activity in a mouse septicemia infection model. Drug-resistant strains of Pseudomonas are a serious health problem, so this family of antibiotics may have important therapeutic applications.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1095-9203
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pubmed:author |
pubmed-author:BernardiniFrancescaF,
pubmed-author:DeMarcoSteven JSJ,
pubmed-author:DiasRicardo L ARL,
pubmed-author:EberlLeoL,
pubmed-author:GombertFrank OFO,
pubmed-author:HenzeHeikoH,
pubmed-author:HunzikerPeterP,
pubmed-author:JetterPeterP,
pubmed-author:KächAndresA,
pubmed-author:LedererAlexanderA,
pubmed-author:MissonPauline EPE,
pubmed-author:ObrechtDanielD,
pubmed-author:RiedelKathrinK,
pubmed-author:RobinsonJohn AJA,
pubmed-author:SchauerStefanS,
pubmed-author:SrinivasNityakalyaniN,
pubmed-author:SteinmannJessicaJ,
pubmed-author:UeberbacherBernhard JBJ,
pubmed-author:Van der MeijdenBenjaminB,
pubmed-author:WerneburgMartinaM,
pubmed-author:ZerbeKatjaK,
pubmed-author:ZieglerUrsU,
pubmed-author:ZumbrunnJürgJ
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
327
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1010-3
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pubmed:dateRevised |
2010-6-9
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pubmed:meshHeading |
pubmed-meshheading:20167788-Animals,
pubmed-meshheading:20167788-Anti-Bacterial Agents,
pubmed-meshheading:20167788-Antimicrobial Cationic Peptides,
pubmed-meshheading:20167788-Bacterial Outer Membrane Proteins,
pubmed-meshheading:20167788-Cell Membrane,
pubmed-meshheading:20167788-Drug Design,
pubmed-meshheading:20167788-Drug Resistance, Bacterial,
pubmed-meshheading:20167788-Genes, Bacterial,
pubmed-meshheading:20167788-Lipopolysaccharides,
pubmed-meshheading:20167788-Mice,
pubmed-meshheading:20167788-Microbial Sensitivity Tests,
pubmed-meshheading:20167788-Molecular Mimicry,
pubmed-meshheading:20167788-Mutation,
pubmed-meshheading:20167788-Peptide Library,
pubmed-meshheading:20167788-Peptides,
pubmed-meshheading:20167788-Protein Structure, Tertiary,
pubmed-meshheading:20167788-Pseudomonas Infections,
pubmed-meshheading:20167788-Pseudomonas aeruginosa,
pubmed-meshheading:20167788-Sepsis
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pubmed:year |
2010
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pubmed:articleTitle |
Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa.
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pubmed:affiliation |
Chemistry Department, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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