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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2005-10-7
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pubmed:abstractText |
Here we show that a new class of antibiotics-acyldepsipeptides-has antibacterial activity against Gram-positive bacteria in vitro and in several rodent models of bacterial infection. The acyldepsipeptides are active against isolates that are resistant to antibiotics in clinical application, implying a new target, which we identify as ClpP, the core unit of a major bacterial protease complex. ClpP is usually tightly regulated and strictly requires a member of the family of Clp-ATPases and often further accessory proteins for proteolytic activation. Binding of acyldepsipeptides to ClpP eliminates these safeguards. The acyldepsipeptide-activated ClpP core is capable of proteolytic degradation in the absence of the regulatory Clp-ATPases. Such uncontrolled proteolysis leads to inhibition of bacterial cell division and eventually cell death.
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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 |
Oct
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:BandowJulia EJE,
pubmed-author:BeyerDieterD,
pubmed-author:Brötz-OesterheltHeikeH,
pubmed-author:EndermannRainerR,
pubmed-author:HenningerKerstinK,
pubmed-author:HinzenBertholdB,
pubmed-author:KrollHein-PeterHP,
pubmed-author:LabischinskiHaraldH,
pubmed-author:LadelChristophC,
pubmed-author:PaulsenHolgerH,
pubmed-author:RaddatzSiegfriedS,
pubmed-author:SahlHans-GeorgHG,
pubmed-author:SchroederWernerW
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1082-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16200071-Animals,
pubmed-meshheading:16200071-Anti-Bacterial Agents,
pubmed-meshheading:16200071-Bacillus subtilis,
pubmed-meshheading:16200071-Bacteria,
pubmed-meshheading:16200071-Depsipeptides,
pubmed-meshheading:16200071-Drug Resistance, Multiple, Bacterial,
pubmed-meshheading:16200071-Endopeptidase Clp,
pubmed-meshheading:16200071-Escherichia coli,
pubmed-meshheading:16200071-Escherichia coli Proteins,
pubmed-meshheading:16200071-Female,
pubmed-meshheading:16200071-Mice,
pubmed-meshheading:16200071-Molecular Structure,
pubmed-meshheading:16200071-Mutation,
pubmed-meshheading:16200071-Pneumococcal Infections,
pubmed-meshheading:16200071-Protein Binding,
pubmed-meshheading:16200071-Protein Processing, Post-Translational,
pubmed-meshheading:16200071-Rats,
pubmed-meshheading:16200071-Rats, Wistar,
pubmed-meshheading:16200071-Sepsis
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pubmed:year |
2005
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pubmed:articleTitle |
Dysregulation of bacterial proteolytic machinery by a new class of antibiotics.
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pubmed:affiliation |
Department of Anti-infectives, Bayer HealthCare AG, Pharma Research, Aprather Weg 18a, D-42096 Wuppertal, Germany. heike.broetz-oesterhelt@bayerhealthcare.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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