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Characterization of the inhibitor-resistant SHV β-lactamase SHV-107 in a clinical Klebsiella pneumoniae strain co-producing GES-7 enzyme

dc.contributor.authorManageiro, Vera
dc.contributor.authorFerreira, Eugénia
dc.contributor.authorCougnoux, Antony
dc.contributor.authorAlbuquerque, Luís
dc.contributor.authorCaniça, Manuela
dc.contributor.authorBonnet, Richard
dc.date.accessioned2013-02-14T17:04:47Z
dc.date.available2013-02-14T17:04:47Z
dc.date.issued2012
dc.description.abstractThe clinical Klebsiella pneumoniae INSRA6884 strain exhibited nonsusceptibility to all penicillins tested (MICs of 64 to>2,048 g/ml). The MICs of penicillins were weakly reduced by clavulanate (from 2,048 to 512 g/ml), and tazobactam restored piperacillin susceptibility. Molecular characterization identified the genes blaGES-7 and a new -lactamase gene, blaSHV-107, which encoded an enzyme that differed from SHV-1 by the amino acid substitutions Leu35Gln and Thr235Ala. The SHV-107-producing Escherichia coli strain exhibited only a -lactam resistance phenotype with respect to amoxicillin, ticarcillin, and amoxicillinclavulanate combination. The kinetic parameters of the purified SHV-107 enzyme revealed a high affinity for penicillins. However, catalytic efficiency for these antibiotics was lower for SHV-107 than for SHV-1. No hydrolysis was detected against oxyimino- -lactams. The 50% inhibitory concentration (IC50) for clavulanic acid was 9-fold higher for SHV-107 than for SHV-1, but the inhibitory effects of tazobactam were unchanged. Molecular dynamics simulation suggested that the Thr235Ala substitution affects the accommodation of clavulanate in the binding site and therefore its inhibitory activity.por
dc.description.sponsorshipThis work was supported financially by the project POCTI/ESP/43037 from Fundação para a Ciência e a Tecnologia, Lisbon, Portugal, awarded to M. Caniça, and by a grant from INRA and Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche (Paris, France), awarded to R. Bonnet. V. Manageiro was supported by grant SFRH/BD/32578/2006 from Fundação para a Ciência e a Tecnologia, Lisbon,Portugal.por
dc.identifier.citationAntimicrob Agents Chemother. 2012 Feb;56(2):1042-6. Epub 2011 Nov 14.por
dc.identifier.issn0066-4804
dc.identifier.otherdoi:10.1128/AAC.01444-10
dc.identifier.urihttp://hdl.handle.net/10400.18/1381
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherAmerican Society for Microbiologypor
dc.relation.publisherversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264250/por
dc.subjectAntibiotic Resistancepor
dc.subjectβ-lactam Inhibitorpor
dc.subjectβ-lactamasepor
dc.subjectESBLpor
dc.subjectInhibitor-resistant SHVpor
dc.subjectResistência aos Antimicrobianospor
dc.titleCharacterization of the inhibitor-resistant SHV β-lactamase SHV-107 in a clinical Klebsiella pneumoniae strain co-producing GES-7 enzymepor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1046por
oaire.citation.startPage1042por
oaire.citation.titleAntimicrobial Agents and Chemotherapypor
oaire.citation.volume56(2)por
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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