Journal
EMBO MOLECULAR MEDICINE
Volume 6, Issue 12, Pages 1622-1637Publisher
WILEY
DOI: 10.15252/emmm.201404309
Keywords
amyloid; curli; EAEC; EHEC; haemolytic uraemic syndrome
Categories
Funding
- European Research Council [ERC- AdG 249780 to RH]
- Deutsche Forschungsgemeinschaft [GRK 1673]
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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-GMPthat 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 degrees 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.
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