Evaluation of Novel Quorum Sensing Inhibitors Targeting Auto-Inducer 2 (AI-2) for the Control of Avian Pathogenic Escherichia coli Infections in Chickens
Yosra A. Helmy, Dipak Kathayat, Löıc Deblais, Vishal Srivastava, Gary Closs, Robert J. Tokarski, Oluwatosin R Ayinde, James R. Fuchs, Gireesh Rajashekara
Abstract
Avian pathogenic Escherichia coli (APEC), a subgroup of ExPEC, is a zoonotic pathogen with public health importance. Quorum sensing is a mechanism that regulates virulence, biofilm formation, and pathogenesis in bacteria. Here, we identified a novel quorum sensing autoinducer-2 inhibitor, QSI-5, which showed higher anti-APEC efficacy in chickens compared to the currently used antibiotic, sulfadimethoxine at a much lower dose (up to 4,500 times). QSI-5 is readily absorbed with no residues in the tissues. QSI-5 also increased the chicken's body weight gain and did not impact the cecal microbiota composition. Overall, QSI-5 represents a promising lead compound for developing novel anti-virulence therapies with significant implications for treating APEC infections in chickens as well as other ExPEC associated infections in humans. Further identification of its target(s) and understanding the mechanism of action of QSI-5 in APEC will add to the future novel drug development efforts that can overcome the antimicrobial resistance problem.