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In this report, we examine the role of zinc limitation in the expression of a virulence factor in uropathogenic <jats:italic>Escherichia coli<\/jats:italic>. The pyelonephritis isolate J96 carries two <jats:italic>hlyCABD<\/jats:italic> operons that encode the RTX toxin \u03b1-hemolysin. While the coding regions of both operons are largely conserved, the upstream sequences, including the promoters, are unrelated. We show here that the two <jats:italic>hlyCABD<\/jats:italic> operons are differently regulated. The <jats:italic>hly<\/jats:italic><jats:sub>\n                  <jats:italic>II<\/jats:italic>\n                <\/jats:sub> operon is efficiently silenced in the presence of zinc and highly expressed when zinc is limited. In contrast, the <jats:italic>hly<\/jats:italic><jats:sub>\n                  <jats:italic>I<\/jats:italic>\n                <\/jats:sub> operon does not respond to zinc limitation. Genetic studies reveal that zinc-responsive regulation of the <jats:italic>hly<\/jats:italic><jats:sub>\n                  <jats:italic>II<\/jats:italic>\n                <\/jats:sub> operon is controlled by the Zur metalloregulatory protein. A Zur binding site was identified in the promoter sequence of the <jats:italic>hly<\/jats:italic><jats:sub>\n                  <jats:italic>II<\/jats:italic>\n                <\/jats:sub> operon, and we observe direct binding of Zur to this promoter region. Moreover, we find that Zur regulation of the <jats:italic>hly<\/jats:italic><jats:sub>\n                  <jats:italic>II<\/jats:italic>\n                <\/jats:sub> operon modulates the ability of <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> J96 to induce a cytotoxic response in host cell lines in culture. Our report constitutes the first description of the involvement of the zinc-sensing protein Zur in directly modulating the expression of a virulence factor in bacteria.<\/jats:p>","DOI":"10.1038\/s41598-018-24964-1","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T13:11:32Z","timestamp":1524143492000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["A new role for Zinc limitation in bacterial pathogenicity: modulation of \u03b1-hemolysin from uropathogenic Escherichia coli"],"prefix":"10.1038","volume":"8","author":[{"given":"Elsa","family":"Velasco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suning","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Sanet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Fern\u00e1ndez-V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Jov\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estibaliz","family":"Glar\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel F.","family":"Valledor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas V.","family":"O\u2019Halloran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4147-219X","authenticated-orcid":false,"given":"Carlos","family":"Balsalobre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,25]]},"reference":[{"key":"24964_CR1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.vetmic.2015.03.024","volume":"179","author":"G Porcheron","year":"2015","unstructured":"Porcheron, G. & Dozois, C. 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