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dc.contributor.authorZarkan, Ashrafen
dc.contributor.authorMacklyne, Heather-Roseen
dc.contributor.authorTruman, Andrew Wen
dc.contributor.authorHesketh, Andrewen
dc.contributor.authorHong, Hee-Jeonen
dc.date.accessioned2015-12-16T15:37:28Z
dc.date.available2015-12-16T15:37:28Z
dc.date.issued2016-01-22en
dc.identifier.citationZarkan et al. Scientific Reports (2016) Vol. 6, Article number 19602. doi:10.1038/srep19602en
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252998
dc.description.abstractVancomycin is a front-line antibiotic used for the treatment of nosocomial infections, particularly those caused by methicillin-resistant Staphylococcus aureus. Despite its clinical importance the global effects of vancomycin exposure on bacterial physiology are poorly understood. In a previous transcriptomic analysis we identified a number of Zur regulon genes which were highly but transiently up-regulated by vancomycin in Streptomyces coelicolor. Here, we show that vancomycin also induces similar zinc homeostasis systems in a range of other bacteria and demonstrate that vancomycin binds to Zn(II) in vitro. This implies that vancomycin treatment sequesters zinc from bacterial cells thereby triggering a Zur-dependent zinc starvation response. The Kd value of the binding between vancomycin and Zn(II) was calculated using a novel fluorometric assay, and NMR was used to identify the binding site. These findings highlight a new biologically relevant aspect of the chemical property of vancomycin as a zinc chelator.
dc.description.sponsorshipThis work was supported by funding from the Royal Society, UK (516002.K5877/ROG), the Medical Research Council, UK (G0700141). A.Z. was supported from the Said foundation and Cambridge Trust.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.titleThe frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II)en
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep19602en
prism.number19602en
prism.publicationDate2016en
prism.publicationNameScientific Reportsen
prism.volume6en
dc.rioxxterms.funderMRC
dc.rioxxterms.projectidG0700141
dcterms.dateAccepted2015-12-14en
rioxxterms.versionofrecord10.1038/srep19602en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-01-22en
dc.contributor.orcidZarkan, Ashraf [0000-0003-3582-124X]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G0700141)


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