Fecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in swine and cattle at slaughter in Switzerland

During the past decade, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have become a matter of great concern in human medicine. ESBL-producing strains are found in the community, not just in hospital-associated patients, which raises a question about possible reservoirs. Recent studies describe the occurrence of ESBL-producing Enterobacteriaceae in meat, fish, and raw milk; therefore, the impact of food animals as reservoirs for and disseminators of such strains into the food production chain must be assessed. In this pilot study, fecal samples of 59 pigs and 64 cattle were investigated to determine the occurrence of ESBL-producing Enterobacteriaceae in farm animals at slaughter in Switzerland. Presumptive-positive colonies on Brilliance ESBL agar were subjected to identification and antibiotic susceptibility testing including the disc diffusion method and E-test ESBL strips. As many as 15.2% of the porcine and 17.1% of the bovine samples, predominantly from calves, yielded ESBL producers. Of the 21 isolated strains, 20 were Escherichia coli, and one was Citrobacter youngae. PCR analysis revealed that 18 strains including C. youngae produced CTX-M group 1 ESBLs, and three strains carried genes encoding for CTX-M group 9 enzymes. In addition, eight isolates were PCR positive for TEM beta-lactamase, but no bla(SHV) genes were detected. Pulsed-field gel electrophoresis showed a high genetic diversity within the strains. The relatively high rates of occurrence of ESBLproducing strains in food animals and the high genetic diversity among these strains indicate that there is an established reservoir of these organisms in farm animals. Further studies are necessary to assess future trends.

Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity

Innate lymphoid cells (ILCs) are critical for maintaining epithelial barrier integrity at mucosal surfaces; however, the tissue-specific factors that regulate ILC responses remain poorly characterized. Using mice with intestinal epithelial cell (IEC)-specific deletions in either inhibitor of κB kinase (IKK)α or IKKβ, two critical regulators of NFκB activation, we demonstrate that IEC-intrinsic IKKα expression selectively regulates group 3 ILC (ILC3)-dependent antibacterial immunity in the intestine. Although IKKβ(ΔIEC) mice efficiently controlled Citrobacter rodentium infection, IKKα(ΔIEC) mice exhibited severe intestinal inflammation, increased bacterial dissemination to peripheral organs, and increased host mortality. Consistent with weakened innate immunity to C. rodentium, IKKα(ΔIEC) mice displayed impaired IL-22 production by RORγt(+) ILC3s, and therapeutic delivery of rIL-22 or transfer of sort-purified IL-22-competent ILCs from control mice could protect IKKα(ΔIEC) mice from C. rodentium-induced morbidity. Defective ILC3 responses in IKKα(ΔIEC) mice were associated with overproduction of thymic stromal lymphopoietin (TSLP) by IECs, which negatively regulated IL-22 production by ILC3s and impaired innate immunity to C. rodentium. IEC-intrinsic IKKα expression was similarly critical for regulation of intestinal inflammation after chemically induced intestinal damage and colitis. Collectively, these data identify a previously unrecognized role for epithelial cell-intrinsic IKKα expression and TSLP in regulating ILC3 responses required to maintain intestinal barrier immunity.