Molecular analysis of the ramRA locus in clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline
Mutations in ramR, a negative regulator of ramA which stimulates transcription of acrA/-B encoding the multidrug efflux pump AcrAB-TolC, were recently shown to result in reduced susceptibility to tigecycline in Klebsiella pneumoniae. We analysed six non-duplicate K. pneumoniae isolates with elevated...
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| Veröffentlicht in: | The New microbiologica 2017-04, Vol.40 (2), p.135-138 |
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| creator | Campos, Cristina Belmar Aepfelbacher, Martin Hentschke, Moritz |
| description | Mutations in ramR, a negative regulator of ramA which stimulates transcription of acrA/-B encoding the multidrug efflux pump AcrAB-TolC, were recently shown to result in reduced susceptibility to tigecycline in Klebsiella pneumoniae. We analysed six non-duplicate K. pneumoniae isolates with elevated MICs to tigecycline. All isolates showed transcriptional up-regulation of ramA and acrB as demonstrated by Northern blot and quantitative real-time PCR. Sequencing of the ramR gene revealed deletions in five of the isolates and a premature stop codon in one isolate. Transformation of the wild-type ramR gene but not of any of the detected mutant ramR genes into a ramR-mutant K. pneumoniae strain restored tigecycline susceptibility and repressed ramA and acrB transcription to wild type levels. Thus, our study confirms the role of inactivating mutations in the ramR gene in tigecycline resistance. |
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We analysed six non-duplicate K. pneumoniae isolates with elevated MICs to tigecycline. All isolates showed transcriptional up-regulation of ramA and acrB as demonstrated by Northern blot and quantitative real-time PCR. Sequencing of the ramR gene revealed deletions in five of the isolates and a premature stop codon in one isolate. Transformation of the wild-type ramR gene but not of any of the detected mutant ramR genes into a ramR-mutant K. pneumoniae strain restored tigecycline susceptibility and repressed ramA and acrB transcription to wild type levels. Thus, our study confirms the role of inactivating mutations in the ramR gene in tigecycline resistance.</description><identifier>ISSN: 1121-7138</identifier><identifier>PMID: 28368073</identifier><language>eng</language><publisher>Italy: Edizioni Medico Scientifiche</publisher><subject>Anti-Bacterial Agents - pharmacology ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Drug Resistance, Bacterial ; Efflux ; Gene Expression Regulation, Bacterial - physiology ; Gene regulation ; Gene sequencing ; Genetic transformation ; Klebsiella ; Klebsiella pneumoniae ; Klebsiella pneumoniae - drug effects ; Klebsiella pneumoniae - genetics ; Minocycline - analogs & derivatives ; Minocycline - pharmacology ; Mutation ; Nonsense mutation ; Stop codon ; Tigecycline ; Transcription</subject><ispartof>The New microbiologica, 2017-04, Vol.40 (2), p.135-138</ispartof><rights>Copyright Edizioni Medico Scientifiche Apr 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28368073$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Campos, Cristina Belmar</creatorcontrib><creatorcontrib>Aepfelbacher, Martin</creatorcontrib><creatorcontrib>Hentschke, Moritz</creatorcontrib><title>Molecular analysis of the ramRA locus in clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline</title><title>The New microbiologica</title><addtitle>New Microbiol</addtitle><description>Mutations in ramR, a negative regulator of ramA which stimulates transcription of acrA/-B encoding the multidrug efflux pump AcrAB-TolC, were recently shown to result in reduced susceptibility to tigecycline in Klebsiella pneumoniae. We analysed six non-duplicate K. pneumoniae isolates with elevated MICs to tigecycline. All isolates showed transcriptional up-regulation of ramA and acrB as demonstrated by Northern blot and quantitative real-time PCR. Sequencing of the ramR gene revealed deletions in five of the isolates and a premature stop codon in one isolate. Transformation of the wild-type ramR gene but not of any of the detected mutant ramR genes into a ramR-mutant K. pneumoniae strain restored tigecycline susceptibility and repressed ramA and acrB transcription to wild type levels. 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| ispartof | The New microbiologica, 2017-04, Vol.40 (2), p.135-138 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Anti-Bacterial Agents - pharmacology Bacterial Proteins - genetics Bacterial Proteins - metabolism Drug Resistance, Bacterial Efflux Gene Expression Regulation, Bacterial - physiology Gene regulation Gene sequencing Genetic transformation Klebsiella Klebsiella pneumoniae Klebsiella pneumoniae - drug effects Klebsiella pneumoniae - genetics Minocycline - analogs & derivatives Minocycline - pharmacology Mutation Nonsense mutation Stop codon Tigecycline Transcription |
| title | Molecular analysis of the ramRA locus in clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline |
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