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