One strategy to prevent infections involves the development of a mucosal vaccine against antigens that are expressed in vivo, present on the bacterial surface, specific to uropathogenic strains, and antigenic. We have used a reverse vaccinology approach involving a large-scale selection process that incorporates bioinformatic, genomic, transcriptomic, and proteomic screens to identify, in an unbiased manner, potential vaccine candidates. Using a murine model of ascending urinary tract infection, we are testing four antigens (Hma IreA, FyuA, IutA), all involved in iron acquisition, for the ability to protect against bladder and kidney infection by uropathogenic strains of E. coli. We are testing all antigens with an array of adjuvants by three different routes (intranasal, subcutaneous, and intramuscular) to determine the best combination of antigens, adjuvant, and route in order to move a specific vaccine formulation to human trials.

In another line of investigation, identification of therapeutic compounds to specifically eradicate uropathogens have been conducted by high throughput screening of chemical libraries and natural product libraries to identify compounds that specifically target iron acquisition systems of bacteria. Novel compounds, including one we named Nicoyamycin A, have been identified and the structure has been elucidated.