QseC Signaling in the Outbreak O104:H4 Strain Combines Multiple Factors during Infection.

Enteroaggregative (EAEC) from the O104:H4 specific serotype caused a large outbreak of bloody diarrhea with some complicated cases of hemolytic-uremic syndrome (HUS) in Europe in 2011. The outbreak strain consisted in an EAEC capable to produce the Shiga toxin (Stx) subtype 2a, a characteristic from enterohemorrhagic QseBC two-component system detects AI-3/Epi/NE and mediates the chemical signaling between pathogen and mammalian host. This system coordinates a cascade of virulence genes expression in important human enteropathogens. The blocking of QseC of EAEC C227-11 (Stx) strain by -phenyl-4-{[(phenylamino) thioxomethyl]amino}-benzenesulfonamide (also known as LED209) demonstrated a lower efficiency of colonization. The periplasmic protein VisP, which is related to survival mechanisms in a colitis model of infection, bacterial membrane maintenance, and stress resistance, here presented high levels of expression during the initial infection within the host. Under acid stress conditions, expression levels were differentiated in an Stx-dependent way. Together, these results emphasize the important role of VisP and the histidine kinase sensor QseC in the C227-11 (Stx) outbreak strain for the establishment of the infectious niche process in the C57BL/6 mouse model and of LED209 as a promising antivirulence drug strategy against these enteric pathogens. EAEC is a remarkable etiologic agent of acute and persistent diarrhea worldwide. The isolates harbor specific subsets of virulence genes and their pathogenesis needs to be better understood. Chemical signaling via histidine kinase sensor QseC has been shown as a potential target to elucidate the orchestration of the regulatory cascade of virulence factors.