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Most cases of campylobacteriosis result from consumption of foods contaminated with undercooked chicken products. The goal of this proposal is to develop a new intervention strategy to reduce the carriage of Campylobacter jejuni in poultry. More specifically, we outline experiments to generate a C. jejuni-blocking agent that will be used in broiler chicks.
Non-Technical Summary: Campylobacter jejuni is the leading cause of bacterial gastroenteritis in the United States, with an estimated cost of treatment and loss of productivity of approximately $8 billion annually. Clinical symptoms of campylobacteriosis consist of fever, severe abdominal cramps and watery diarrhea or a dysentery-like syndrome typical of shigellosis. Chicken products are the primary foods in which C. jejuni is disseminated to humans. Our working hypothesis is that C. jejuni constitutively synthesizes a subset of proteins, termed adhesins, that facilitate the organism's binding to the cells lining the intestinal tract of chickens, and other reservoir hosts in which they cause no disease symptoms. Therefore, our ultimate goal is to reduce human exposure to C. jejuni by reducing the numbers of chickens colonized with C. jejuni. The specific goal of this project is to characterize one C. jejuni adhesin termed CadF, which has already been proven to play an essential role in the colonization of chickens by C. jejuni, and to assess whether the CadF protein can be used as a probiotic to block C. jejuni colonization. <P> Approach: In vivo experiments with C. jejuni and a cadF null mutant indicate that CadF is required for the colonization of newly hatched Leghorn chickens. Caulobacter crescentus is a harmless bacterium that exhibits a surface protein arranged in a two dimensional crystal that can be modified by the addition of large foreign peptide inserts. Here we outline the methods and experiments required to generate a blocking agent based on high-density display of CadF regions on the surface of C. crescentus. The specific aims are to: 1) characterize the in vitro binding properties (e.g., to Fn and host cells) of C. crescentus presenting several peptide forms of the C. jejuni CadF Fn-binding domain; 2) identify the binding target of CadF in both human and chicken Fn and examine host cell signaling pathways altered in response to Fn binding; and 3) determine whether chicks provided with a feed supplemented with CadF-presenting C. crescentus are protected from C. jejuni challenge.