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dc.contributor.authorBolard, Arnaud
dc.contributor.authorSchniederjans, Monika
dc.contributor.authorHaussler, Susanne
dc.contributor.authorTriponney, Pauline
dc.contributor.authorValot, Benoît
dc.contributor.authorPlesiat, Patrick
dc.contributor.authorJeannot, Katy
dc.date.accessioned2019-08-13T11:59:00Z
dc.date.available2019-08-13T11:59:00Z
dc.date.issued2019-08-05
dc.identifier.citationAntimicrob Agents Chemother. 2019 Aug 5. pii: AAC.01044-19. doi: 10.1128/AAC.01044-19.en_US
dc.identifier.issn1098-6596
dc.identifier.pmid31383668
dc.identifier.doi10.1128/AAC.01044-19
dc.identifier.urihttp://hdl.handle.net/10033/621899
dc.description.abstractEmergence of resistance to polymyxins in Pseudomonas aeruginosa is mainly due to mutations in two-components systems, that promote addition of 4-amino-4-deoxy-L-arabinose to the lipopolysaccharide (LPS) through upregulation of operon arnBCADTEF-ugd (arn) expression. Here, we demonstrate that mutations occurring in different domains of histidine kinase PmrB or in response regulator PmrA result in coresistance to aminoglycosides and colistin. All seventeen clinical strains tested exhibiting such a cross-resistance phenotype were found to be pmrAB mutants. As shown by gene deletion experiments, the decreased susceptibility of the mutants to aminoglycosides was independent from operon arn but required the efflux system MexXY(OprM) and the products of three genes, PA4773-PA4774-PA4775, that are cotranscribed and activated with genes pmrAB Gene PA4773 (annotated as speD2 in PAO1 genome) and PA4774 (speE2) are predicted to encode enzymes involved in biosynthesis of polyamines. Comparative analysis of cell surface extracts of an in vitro selected pmrAB mutant, called AB16.2, and derivatives lacking PA4773, PA4774 and PA4775, respectively revealed that these genes were needed for norspermidine production via a pathway that likely uses 1,3-diaminoprane, a precursor of polyamines. Altogether, our results suggest that norspermidine decreases the self-promoted uptake pathway of aminoglycosides across the outer membrane and thereby potentiates the activity of efflux pump MexXY(OprM).en_US
dc.language.isoenen_US
dc.publisherAmerican Society of microbiologyen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleProduction of norspermidine contributes to aminoglycoside resistance in pmrAB mutants of Pseudomonas aeruginosa.
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalAntimicrobial agents and chemotherapyen_US
refterms.dateFOA2019-08-13T11:59:00Z
atmire.accessrights
dc.source.journaltitleAntimicrobial agents and chemotherapy


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