Novel Anti-virulence Compound to Control Avian Pathogenic Escherichia coli (APEC) Infections in Poultry

Colibacillosis caused by APEC is associated with high morbidity, mortality and production losses, leading to sever economic losses. APEC can be transmitted to humans through consumption of contaminated poultry products. APEC infections are currently controlled through vaccination or antibiotic treatment; however, limited effect of vaccine and emergence antibiotic resistant strains have necessitated the development of novel therapeutics. Here, we tested the APEC quorum sensing inhibitors (QSI-1, 2, 5-8, and 10), that were identified earlier from our in vitro studies, in chickens (n= 6) to reduce APEC infection. QS inhibitors were administered orally (1 mg/kg body weight) and chickens were challenged with APEC subcutaneously. QSI-5 conferred best protection [100% reduction in mortality, 82%-93% reduction in lesions (airsacculitis, perihepatitis, peritonitis, pericarditis) severity, and 5.2-6.1 logs reduction in APEC load]. QSI-5 was further tested in chickens (n= 115) raised on built-up floor litter at the optimal dose (1mg/L) in drinking water, mimicking industry practice. QSI-5 reduced the mortality by 72.2%, lesion severity up to 88.4%, and APEC load up to 2.8 logs, which was better than the reduction observed with currently used antibiotic sulfadimethoxine. QSI-5 was detected in chicken's blood after 0.5h with no detectable residues in muscle, liver and kidney. QSI-5 did not impact the body weight gain, feed conversion ratio, and cecal microbiota of the treated chickens. In conclusion, QSI-5 displayed promising effect in chickens and thus represents a novel anti-APEC therapeutic. Our future studies will focus on testing the QSI-5 in field and identification of the antibacterial target.