Mutating both and of enteropathogenic E2348/69 attenuates its virulence and induces interleukin 6 .

Here, we report for the first time that disrupting both and genes in enteropathogenic E2348/69 can attenuate its virulence and significantly induce interleukin 6 (IL-6) . Our experimental analyses demonstrated that an E2348/69 ΔΔ double mutant strain derepressed the expression of type IV bundle forming pilus (BFP) and repressed the expression of glutamate decarboxylase (GAD) and locus of enterocyte effacement (LEE). Whole genome-scale transcriptomic analysis revealed that 1,564 EPEC genes were differentially expressed in the ΔΔ double mutant strain (cut-off > two-fold). Such depletion of and attenuated the virulence of E2348/69 in a infection model. Surprisingly, IL-6 was highly induced in porcine macrophages infected with the ΔΔ double mutant strain compared to those with its wildtype strain. Coinciding with these results, murine peritoneal challenge assays showed high increase of IL-6 and improved bacterial clearance in response to infection by the ΔΔ double mutant strain. Taken together, our data suggest that and play an essential role in regulating biological processes during EPEC pathogenesis and that their depletion can affect host immune responses by inducing IL-6.