Avian pathogenic E. coli (APEC) is one of the most common bacterial infections affecting the poultry industry. APEC infections cause several extra-intestinal diseases, referred to as avian colibacillosis, that affect at least 30% of commercial flocks in the US. These infections lead to significant mortality and decreased meat and egg production, resulting in multi-million-dollar losses to the poultry industry each year. Additionally, APEC has been identified as a source of human foodborne pathogen, resulting in extra-intestinal infections, such as urinary tract infections and meningitis in humans. Therefore, APEC represents a concern to both animal and human health. Currently, antibiotics are the most common method used to control APEC infections in poultry flocks. However, antibacterial resistance has been reported in several APEC strains in the world’s leading poultry producing countries. Therefore, the development of new antibacterials to circumvent the increasing concern of antibacterial resistance is crucial to maintaining sustainable food production, reducing economic losses, and promoting food security and safety. In this research, novel antibacterial small molecules and peptides have been identified that display both in vitro activity through disruption of the bacterial outer membrane and in vivo activity against APEC in chickens. Various synthetic strategies have been utilized to generate sufficient quantities of these compounds for both in vitro and in vivo biological evaluation as well as the generation of structural analogues and biotinylated probe molecules for use in structure-activity relationship studies and affinity based pull-down experiments for target confirmation.

Synthesis and biological evaluation of novel antibacterial small molecules and peptides against APEC

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