Mechanisms of Antibiotic Efflux in Campylobacter

Non-Technical Summary: Campylobacter jejuni, an important foodborne pathogen causing gastroenteritis in humans, has evolved multiple mechanisms to counteract the action of various antibiotics, which has posed a serious threat to public health. Many of these resistance mechanisms, such as gyrA mutations and Beta-lactamase production, confer Campylobacter resistance to specific antibiotics. However, the active efflux systems, which extrude structurally diverse antibiotics out of bacterial cells, contributes to the intrinsic and acquired resistance to multiple drugs. Although previous studies suggested the possible presence of functional efflux systems in C. jejuni, the antibiotic efflux machinery in this pathogen has not been defined. The purpose of this study is to define the functions of the efflux systems and their regulation by transcriptional factors. <P> Approach: Various genetic and biochemical approaches, including random and site-specific mutagenesis, recombinant proteins, substrate accumulation assay, and DNA binding assay, will be utilized to define the functions of the efflux systems and their interplay with regulatory proteins.