title: Cyclic-di-GMP signalling and biofilm-related properties of the Shiga toxin-producing 2011 German outbreak Escherichia coli O104:H4.
abstract: In 2011, nearly 4,000 people in Germany were infected by Shiga toxin (Stx)-producing Escherichia coli O104:H4 with > 22% of patients developing haemolytic uraemic syndrome (HUS). Genome sequencing showed the outbreak strain to be related to enteroaggregative E. coli (EAEC), suggesting its high virulence results from EAEC-typical strong adherence and biofilm formation combined to Stx production. Here, we report that the outbreak strain contains a novel diguanylate cyclase (DgcX)--producing the biofilm-promoting second messenger c-di-GMP--that shows higher expression than any other known E. coli diguanylate cyclase. Unlike closely related E. coli, the outbreak strain expresses the c-di-GMP-controlled biofilm regulator CsgD and amyloid curli fibres at 37°C, but is cellulose-negative. 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-di-GMP 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.
authors.affiliation: Institute of Biology / Microbiology Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Anja M
authors.initials: AM
authors.lastname: Richter
authors.affiliation: Institute of Biology / Microbiology Humboldt-Universität zu Berlin, Berlin, Germany.
authors.forename: Tatyana L
authors.initials: TL
authors.lastname: Povolotsky
authors.affiliation: Institute of Microbiology and Epizootics Freie Universität Berlin, Berlin, Germany.
authors.forename: Lothar H
authors.initials: LH
authors.lastname: Wieler
authors.affiliation: Institute of Biology / Microbiology Humboldt-Universität zu Berlin, Berlin, Germany Regine.hengge@hu-berlin.de.
authors.forename: Regine
authors.initials: R
authors.lastname: Hengge
mesh_terms: D018441:Biofilms; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004196:Disease Outbreaks; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005858:Germany / Q000453:epidemiology; D006463:Hemolytic-Uremic Syndrome / Q000453:epidemiology / Q000382:microbiology*; D006801:Humans; D008875:Middle Aged; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism; D022621:Shiga Toxin; D054323:Shiga-Toxigenic Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*
chemical_list: D029968:Escherichia coli Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D022621:Shiga Toxin; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP
keywords: EAEC; EHEC; amyloid; curli; haemolytic uraemic syndrome