No abstract

Escherichia coli O157:H7 is an important pathogen of humans. Cattle are most frequently identified as the primary source of infection, and therefore, reduction in E. coli O157:H7 prevalence in cattle by vaccination represents an attractive strategy for reducing the incidence of human disease. H7 flagella have been implicated in intestinal-epithelial colonization of E. coli O157:H7 and may represent a useful target for vaccination. In this study, calves were immunized either systemically with H7 flagellin by intramuscular injection or mucosally via the rectum with either H7 or H7 incorporated into poly(DL-lactide-co-glycolide) microparticles (PLG:H7). Systemic immunization resulted in high levels of flagellin-specific immunoglobulin G (IgG) and IgA in both serum and nasal secretions and detectable levels of both antibody isotypes in rectal secretions. Rectal administration of flagellin resulted in levels of rectal IgA similar to those by the intramuscular route but failed to induce any other antibody response, whereas rectal immunization with PLG:H7 failed to induce any H7-specific antibodies. Following subsequent oral challenge with E. coli O157:H7, reduced colonization rates and delayed peak bacterial shedding were observed in the intramuscularly immunized group compared to nonvaccinated calves, but no reduction in total bacterial shedding occurred. Rectal immunization with either H7 or PLG:H7 had no effect on subsequent bacterial colonization or shedding. Furthermore, purified H7-specific IgA and IgG from intramuscularly immunized calves were shown to reduce intestinal-epithelial binding in vitro. These results indicate that H7 flagellin may be a useful component in a systemic vaccine to reduce E. coli O157:H7 colonization in cattle.Enterohemorrhagic Escherichia coli (EHEC) is a zoonotic pathogen of worldwide importance, causing severe diarrhea (hemorrhagic colitis) and, in a small percentage of cases, hemolytic-uremic syndrome in humans. Ruminants are an important reservoir of EHEC, and human infections are frequently associated with direct or indirect contact with ruminant feces, particularly those derived from cattle (16,26,34,36). Coincidentally, strategies to reduce the carriage of EHEC in ruminants are predicted to lower the incidence of human disease (reviewed in reference 36), and stochastic simulation models predict that cattle are a key control point to reduce EHEC infections in humans (22).An attractive strategy to reduce EHEC colonization in cattle is by vaccination. A number of EHEC vaccines have been evaluated in cattle and have primarily focused on immunization with bacterial proteins encoded by genes located within the locus of enterocyte effacement (LEE) that are known to play key roles in EHEC colonization of the bovine intestine (7,13,32,41). These include immunization with recombinant EspA (14), recombinant intimin (40), and a secreted protein preparation containing Tir and proteins of the type III secretion system (35). In addition, immunization with recombinant EHEC factor for adherence (...

Graphical abstract

accession numbers: JN596964 (Cy-gala-ash), JN596966 (Cy-gala-cat), JN596967 (Cy-

noted between milk and serum Ca (0.17), Mo (0.19), and Na (−0.79). Additional multivariate analyses between measures within sample type (i.e., milk or serum) revealed significant positive associations, both phenotypic and genetic, between some of the elements. In milk, Se was genetically correlated with Ca (0.63), Mg (0.59), Mn (0.40), P (0.53), and Zn (0.52), whereas in serum, V showed strong genetic associations with Cd (0.71), Ca (0.53), Mn (0.63), Mo (0.57), P (0.42), K (0.45), and Hg (−0.44). These results provide evidence that element concentrations in milk and blood of dairy cows are significantly influenced by both diet and genetics and demonstrate the potential for genetic selection and dietary manipulation to alter nutrient concentration to improve both cow health and the healthfulness of milk for human consumption.