JAL participated in the study design and manuscript revisions. All authors read and approved the final manuscript.”
“Background Escherichia coli (E. coli) O157 (O157) was first identified as a human enteric

pathogen in 1982 and has since been implicated in several outbreaks and sporadic infections [1, 2]. Currently, this human pathogen ranks fourth after Campylobacter, Salmonella, and Shigella among the etiologic agents causing diarrhea in North America [3, 4]. Cattle are the primary reservoirs for O157, with the bovine recto-anal Wnt inhibitors clinical trials junction (RAJ) serving as the primary colonization site for O157. Humans acquire infection by consumption of undercooked beef products such as ground meat or foods contaminated with manure [1, 2]. The bovine RAJ comprises of two cell types, the follicle associated epithelium (FAE) towards the distal colon and the stratified squamous epithelium (RSE) closer to the anal canal [5]. Thus far, studies analyzing O157 persistence Angiogenesis inhibitor at the RAJ have focused primarily

on its interactions with the FAE cells [6, 7]. Proteins encoded on the O157 pathogenicity island, Locus of Enterocyte Effacement (LEE), have been shown to play a critical role in O157 adherence to FAE cells. These include the E. coli secreted proteins EspA and EspB, the adhesin Intimin, and the translocated receptor for Intimin, Tir which is secreted via the LEE-encoded type III secretion system (TTSS) [6–8]. Hence, several pre-harvest control measures being evaluated in cattle to control or eliminate O157 from entering the food chain [9–14], include vaccines targeting these LEE-encoded proteins. For instance, Potter et al. developed a vaccine comprising wild-type O157 culture supernatants that contain the TTSS proteins, Tir and Esps [15]; however, similar protection was noted in animals inoculated with the culture selleck inhibitor supernatant from a mutant strain of O157 lacking the tir gene. In addition, the immune response of the vaccinated animals was not merely to the TTSS proteins but also against a number of other proteins

that were present in the supernatant. Interestingly, although the vaccine decreased both the number of E. coli O157 shed in the feces of vaccinated animals, and those colonizing the terminal rectum, it did not reduce the duration of shedding despite the subcutaneous administration of three doses of the vaccine [15, 16]; http://​www.​bioniche.​com. Similar results were also observed with another vaccine that targets the O157 siderophore receptor and porin (SRP) proteins [17, 18]; https://​animalhealth.​pfizer.​com. This clearly suggests that unidentified proteins other than those constituting the TTSS or SRP may play a crucial role in bovine colonization, and that the identification and inclusion of such proteins is likely to increase the efficacy of vaccines for elimination of O157 from the gastrointestinal tracts of cattle.