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Genome sequencing showed the outbreak strain to be related to enteroaggregative\n                    <jats:italic>E.\u00a0coli<\/jats:italic>\n                    (EAEC), suggesting its high virulence results from EAEC\u2010typical strong adherence and biofilm formation combined to Stx production. Here, we report that the outbreak strain contains a novel diguanylate cyclase (DgcX)\u2014producing the biofilm\u2010promoting second messenger c\u2010di\u2010GMP\u2014that shows higher expression than any other known\n                    <jats:italic>E.\u00a0coli<\/jats:italic>\n                    diguanylate cyclase. Unlike closely related\n                    <jats:italic>E.\u00a0coli<\/jats:italic>\n                    , the outbreak strain expresses the c\u2010di\u2010GMP\u2010controlled biofilm regulator CsgD and amyloid curli fibres at 37\u00b0C, but is cellulose\u2010negative. Moreover, it constantly generates derivatives with further increased and deregulated production of CsgD and curli. Since curli fibres are strongly proinflammatory, with cellulose counteracting this effect, high c\u2010di\u2010GMP and curli production by the outbreak O104:H4 strain may enhance not only adherence but may also contribute to inflammation, thereby facilitating entry of Stx into the bloodstream and to the kidneys where Stx causes HUS.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201404309","type":"journal-article","created":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T03:49:02Z","timestamp":1414813742000},"page":"1622-1637","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Cyclic\u2010di\u2010GMP signalling and biofilm\u2010related properties of the Shiga toxin\u2010producing 2011 German outbreak Escherichia coli O104:H4"],"prefix":"10.1038","volume":"6","author":[{"given":"Anja M","family":"Richter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana L","family":"Povolotsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothar H","family":"Wieler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regine","family":"Hengge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,10,31]]},"reference":[{"key":"BFEMMM201404309_CR1","doi-asserted-by":"crossref","first-page":"e41628","DOI":"10.1371\/journal.pone.0041628","volume":"7","author":"R Al Safadi","year":"2012","unstructured":"Al Safadi R, Abu\u2010Ali GS, Sloup RE, Rudrik JT, Waters CM, Eaton KA, Manning SD (2012) Correlation between in vivo biofilm formation and virulence gene expression in Escherichia coli O104:H4. 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