Siderophore-mediated iron acquisition has been targeted for iron-dependent pathogen control given its critical role in bacterial pathogenesis. Enterobactin (Ent), a representative catecholate siderophore that has the highest affinity for ferric iron, is an archetype for iron acquisition in Gram- negative bacteria. Our recent studies have revealed novel features of Ent-mediated acquisition in Campylobacter, a leading bacterial cause of human gastroenteritis in the United States. More importantly, our findings indicate that Campylobacter is an ideal model organism to examine catecholates-mediated iron acquisition and to explore innovative strategy of iron-dependent control. Lipocalins, the soluble host acute phase proteins, have been demonstrated to function as an innate bacteriostatic agent to control Gram-negative infections by interfering with Ent-mediated iron acquisition through their potent Ent-binding ability. This evidence together with our preliminary studies, particularly the successful production of Ent specific antibodies, prompted us to hypothesize that Campylobacter can utilize various catecholate siderophores and Ent specific antibodies function as an effective bacteriostatic agent against Campylobacter infection. To test this, we plan to 1) determine utilization of various catecholate siderophores by Campylobacter and examine inhibitory effect of Ent antibodies on catecholates-dependent growth of Campylobacter; and 2) evaluate in vivo efficacy of Ent antibodies- based immune intervention strategies in a chicken model of C. jejuni infection. This project will not only improve our understanding of Ent-mediated high affinity iron acquisition in Campylobacter but also result in major conceptual advances in the development of new vaccine and therapeutics against C. jejuni and other Gram-negative pathogens.
Campylobacter species are the most prevalent foodborne bacterial pathogen causing human gastroenteritis in the U.S. This project will provide critical information for developing innovative iron- dependent control against Campylobacter and other Gram-negative pathogens to protect public health.
