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My overall research goal is to study molecular mechanisms of bacterial pathogenesis and drug resistance, which will reveal potential targets for development of novel intervention strategies and diagnostic tools against pathogens important in animal health and food safety/security.<P> Objectives: <OL> <LI> Focus on emerging diseases - Identify, characterize and develop improved detection methods related to newly recognized, novel or emerging causes of zoonotic enteric diseases and enteric pathogens of cattle and swine. <LI>Focus on effective interventions - Develop and improve interventions and preventative measures to reduce the incidence and prevalence of infections of cattle and swine with enteric and food borne disease agents.</OL> The specific objectives are:<OL> <LI> To study high-affinity siderophore-mediated iron scavenging for Campylobacter infection.<LI> To determine molecular basis of antimicrobial peptide reisstance in Campylobacter. <LI> To elucidate antibiotic resistance gene reservoir in gut microbiota and corresponding mechanisms and transmission of antimicrobial resistance. <LI> To examine effect of antibiotic growth promoters on intestinal microbiota in food animals.
Non-Technical Summary: The estimated cases of campylobacteriosis in the United States are more than 2 million per year. The medical and productivity costs resulting from C. jejuni infection are estimated at $1.5 to $8.0 billion dollars each year in the United States. Epidemiologic studies have revealed that poultry are the major reservoir of C. jejuni, and consumption of undercooked chickens or food contaminated by poultry products are responsible for the majority of human Campylobacter enteritis. Increasing evidence also indicates that antibiotic use in poultry selects for resistant strains of C. jejuni, posing a significant threat to public health. Thus, on-farm control of C. jejuni is urgently needed to reduce human exposure and the number of foodborne illness in the U.S. Specifically, this project has following expected impacts. Impact 1. Campylobacter jejuni, the most prevalent foodborne human pathogen, is the leading bacterial cause of human gastroenteritis in the U.S. Research in this lab focuses on the development of innovative strategies to control Campylobacter infection in humans and in animal reservoirs, consequently reducing the occurrence of foodborne illness. Impact 2. Emergence of bacterial antibiotic resistance has become a serious problem worldwide. Research in this lab will elucidate the mechanisms for the development, persistence, and transfer of antibiotic resistance in zoonotic foodborne human pathogens. The studies may open new avenues for treatment and prevention of resistant foodborne pathogens important in animal health and food safety. Impact 3. Zoonotic human pathogens (e.g. Campylobacter) could be used as biological agents in acts of terrorism. Thus, research in this lab is also significant in biodefense. The studies will provide important information to develop effective vaccines, diagnostics and therapeutics to protect the public health. Impact 4. Research on the effects of antibiotic growth promoter on intestinal microbiota will lead to development of alternative microbiota-based strategies for promoting growth of food animals, which has significant impact on the production, sustainability, and health of food animals. <P> Approach: Both fundamental and contemporary approaches will be used in this project to study Campylobacter jejuni, the leading foodborne human pathogen causing enteritis in the United States and many other industrialized countries. Specifically, we will use a panel of genetic, genomics and bioinformatics approaches to achieve our goal, such as site-directed mutagenesis, random transposon mutagenesis, microarray, transformation, conjugation, quantitative Real-Time RT-PCR, Phylochips, and pyrosequencing. A powerful chicken model will be for studying mechanisms of pathogenesis and antibiotic resistance in Campylobacter and also will be used for developing innovative vaccines against Campylobacter.