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dc.contributor.authorZafar, Munira
dc.contributor.authorJahan, Humera
dc.contributor.authorShafeeq, Sulman
dc.contributor.authorNimtz, Manfred
dc.contributor.authorJänsch, Lothar
dc.contributor.authorRömling, Ute
dc.contributor.authorChoudhary, M Iqbal
dc.date.accessioned2020-09-10T12:37:23Z
dc.date.available2020-09-10T12:37:23Z
dc.date.issued2020-08-24
dc.identifier.citationInfect Immun. 2020;IAI.00510-20. doi:10.1128/IAI.00510-20.en_US
dc.identifier.pmid32839186
dc.identifier.doi10.1128/IAI.00510-20
dc.identifier.urihttp://hdl.handle.net/10033/622438
dc.description.abstractUpon biofilm formation, production of extracellular matrix components and alteration in physiology and metabolism allows bacteria to build up multicellular communities which can facilitate nutrient acquisition during unfavorable conditions and provide protection towards various forms of environmental stresses to individual cells. Thus, bacterial cells become tolerant against antimicrobials and the immune system within biofilms. In the current study, we evaluated the antibiofilm activity of the macrolides clarithromycin and azithromycin. Clarithromycin showed antibiofilm activity against rdar (red, dry and rough) biofilm formation of the gastrointestinal pathogen Salmonella typhimurium ATCC14028 Nalr at 1.56 μM subinhibitory concentration in standing culture and dissolved cell aggregates at 15 μM in a microaerophilic environment suggesting that the oxygen level affects the activity of the drug. Treatment with clarithromycin significantly decreased transcription and production of the rdar biofilm activator CsgD, with biofilm genes such as csgB and adrA to be consistently downregulated. While fliA and other flagellar regulon genes were upregulated, apparent motility was downregulated. RNA sequencing showed a holistic cell response upon clarithromycin exposure, whereby not only genes involved in the biofilm-related regulatory pathways, but also genes that likely contribute to intrinsic antimicrobial resistance, and the heat shock stress response were differentially regulated. Most significantly, clarithromycin exposure shifts the cells towards an apparent oxygen- and energy- depleted status, whereby the metabolism that channels into oxidative phosphorylation is downregulated, and energy gain by degradation of propane 1,2-diol, ethanolamine and L-arginine catabolism, potentially also to prevent cytosolic, is upregulated. This analysis will allow the subsequent identification of novel intrinsic antimicrobial resistance determinants.en_US
dc.language.isoenen_US
dc.publisherASMen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleClarithromycin Exerts an Antibiofilm Effect against rdar Biofilm Formation, and Transforms the Physiology towards an Apparent Oxygen-depleted Energy and Carbon Metabolism.en_US
dc.typeArticleen_US
dc.identifier.eissn1098-5522
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalInfection and immunityen_US
refterms.dateFOA2020-02-24T00:00:00Z
dc.source.journaltitleInfection and immunity
dc.source.countryUnited States


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