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The main objectives of this application are to determine the molecular genetic basis underlying the rapid development of fluoroquinolone-resistant Campylobacter jejuni in chickens and to elucidate how acquisition of fluoroquinolone resistance affects the in-host fitness of this organism.
NON-TECHNICAL SUMMARY: Campylobacter jejuni is a major foodborne pathogen in the United States. This pathogen is increasingly resistant to fluoroquinololones (FQs), a major antibiotic used for treatment of Campylobacter infections in humans. Despite the recent advances in understanding the development and biological fitness of FQ-resistant Campylobacter, the molecular basis underlying the rapid emergence of FQ-resistant Campylobacter in animal reservoirs and how acquisition of FQ resistance affects Campylobacter fitness are still unknown. The purpose of this study is to determine the molecular genetic mechanisms underlying the rapid emergence and enhanced fitness of FQ-resistant Campylobacter in chickens. The findings will facilitate the design of strategies to prevent the emergence and transmission of FQ-resistant Campylobacter.<P>APPROACH: Contemporary molecular approaches, an animal model (chicken), and conventional microbiological methods will be utilized in this project. The molecular techniques to be used include polymerase chain reaction, gene cloning, mutagenesis, and gene expression analysis. In vivo treatment and pairwise competitions will be utilized to assess the emergence and fitness of fluoroquinolone-resistant Campylobacter in chickens. Statistical methods will be used for data analysis.