Evaluation of Novel Quorum Sensing Inhibitors Targeting Auto-Inducer 2 (AI-2) for the Control of Avian Pathogenic Escherichia coli Infections in Chickens.

Avian pathogenic Escherichia coli (APEC) associated with colibacillosis results in high morbidity and mortality, and severe economic losses to the poultry industry. APEC is a zoonotic pathogen and can infect humans through contaminated poultry products. Vaccination and antibiotic treatment are currently used to control APEC infections; however, the limited effect of vaccines and the emergence of antibiotic-resistant strains have necessitated the development of novel therapeutics. Here, we evaluated seven quorum sensing inhibitors (QSI) identified in our previous study, in APEC-infected chickens. QSIs were administered orally (~92 to 120 μg/bird) and chickens were challenged subcutaneously with APEC. Among them, QSI-5 conferred the best protection (100% reduction in mortality, 82% to 93% reduction in lesions [airsacculitis, perihepatitis, lung congestion, pericarditis] severity, and 5.2 to 6.1 logs reduction in APEC load). QSI-5 was further tested in chickens raised on built-up floor litter using an optimized dose (1 mg/L) in drinking water. QSI-5 reduced the mortality (88.4%), lesion severity (72.2%), and APEC load (2.8 logs) in chickens, which was better than the reduction observed with currently used antibiotic sulfadimethoxine (SDM; mortality 35.9%; lesion severity up to 36.9%; and APEC load up to 2.4 logs). QSI-5 was detected in chicken's blood after 0.5 h with no residues in muscle, liver, and kidney. QSI-5 increased the body weight gain with no effect on the feed conversion ratio and cecal microbiota of the chickens. Metabolomic studies revealed reduced levels of 5'-methylthioadenosine in QSI-5-treated chicken serum. In conclusion, QSI-5 displayed promising effects in chickens and thus, represents a novel anti-APEC therapeutic.