Efficacy and safety evaluation of artificial intelligence-identified antimicrobial peptides targeting avian pathogenic Escherichia coli in broiler chickensOA
Background The overuse of antibiotics in both veterinary and human medicine has resulted in the emergence of antibiotic-resistant bacteria,prompting a search for effective alternatives.Antimicrobial peptides(AMPs)are short,often cationic,peptide-based molecules with antimicrobial and immunomodulatory activity,which makes them promising alternatives to conventional antibiotics in poultry production.Results From a prior machine-learning-guided screen of 875 candidate AMPs against a wide bacterial panel,62exhibited activity against avian pathogenic Escherichia coli(APEC)and low in vitro hemolytic and cytotoxic activity.We selected three lead AMPs from this list(named TeRu4,TeBi1,and PeNi4),and evaluated their in vitro and in vivo efficacy,safety,and immunomodulatory potential for use in poultry farming.In animal experiments,AMPs were administered via in ovo injection on d 18 of embryonic development.In APEC challenge trials,yolk sacs were inoculated with APEC post-hatch to assess early chick mortality,while in pen trials,birds were raised in a commercial production setting for 35 d.For challenged birds,TeBi1(10μg/egg)significantly reduced culture-positive rates for APEC in the air sac and pericardium,increased body weight by 50%and reduced cytokine transcript levels by 10%-30%on d 7post hatch.In HD11 chicken macrophage-like cultured cells,TeRu4(16μg/mL)suppressed lipopolysaccharide(LPS)-induced pro-inflammatory cytokine transcript levels.In pen trials,TeRu4(20μg/egg)increased the survival probability of female birds by 4.9%,while TeBi1(20μg/egg)increased the survival probability of all birds by 4.4%,by d 35.Gene expression analysis revealed AMP-and sex-specific cytokine responses.In pen trials,no significant differences were observed in mean weights,feed conversion ratio(FCR),and flock uniformity on d 35.By integrating high-throughput in ovo automation with large-scale commercial pen trials,this study provides a systematic translational bridge from in silico AI discovery to field-relevant poultry production interventions.Conclusions These findings demonstrate that TeBi1 and TeRu4 are promising antibiotic alternatives that improve survival,modulate immune responses,and maintain normal growth performance in broiler chickens in this experimental setting.
Emre Demirsoy;Teagan I.Parkin;Shaeleen E.Mihalynuk;Anna H.Dema;Lorissa Corrie;Marika E.Heilker;Haley N.Kuecks‑Winger;Anat Yanai;Uluc B.Birol;Michael McIlwee;Kay de Wet;Mathijs Knipscheer;Victoria Bowes;Vanessa Tuytel;Liam Ritchie;Wolfgang Koster;Emil Berberov;William R.Cox;Monica Kotkoff;Vanessa C.Thompson;Rene L.Warren;Erin Fraser;Linda M.N.Hoang;Fraser Hof;Fatih Birol;Caren C.Helbing;Inanc Birol
BC Cancer,Vancouver,BC V5Z 1L3,Canada British Columbia Centre for Disease Control,Public Health Laboratory,Vancouver,BC V6Z R4R,Canada Genome Science and Technology Graduate Program,University of British Columbia,Vancouver,BC V6T 1Z4,CanadaDepartment of Biochemistry and Microbiology,University of Victoria,Victoria,BC V8P 5C2,CanadaDepartment of Biochemistry and Microbiology,University of Victoria,Victoria,BC V8P 5C2,CanadaDepartment of Biochemistry and Microbiology,University of Victoria,Victoria,BC V8P 5C2,CanadaDepartment of Biochemistry and Microbiology,University of Victoria,Victoria,BC V8P 5C2,CanadaDepartment of Biochemistry and Microbiology,University of Victoria,Victoria,BC V8P 5C2,CanadaDepartment of Biochemistry and Microbiology,University of Victoria,Victoria,BC V8P 5C2,CanadaCanada’s Michael Smith Genome Sciences Centre at BC Cancer,Vancouver,BC V5Z 4S6,Canada Amphoraxe Life Sciences Inc.,Vancouver,BC V6L 3C9,CanadaAmphoraxe Life Sciences Inc.,Vancouver,BC V6L 3C9,CanadaSJ Ritchie Research Farms,Abbotsford,BC V4X 2N4,CanadaSJ Ritchie Research Farms,Abbotsford,BC V4X 2N4,CanadaSJ Ritchie Research Farms,Abbotsford,BC V4X 2N4,CanadaSJ Ritchie Research Farms,Abbotsford,BC V4X 2N4,CanadaSJ Ritchie Research Farms,Abbotsford,BC V4X 2N4,CanadaSJ Ritchie Research Farms,Abbotsford,BC V4X 2N4,CanadaVaccine and Infectious Disease Organization(VIDO),University of Saskatchewan,Saskatoon,SK S7N 5E3,CanadaVaccine and Infectious Disease Organization(VIDO),University of Saskatchewan,Saskatoon,SK S7N 5E3,CanadaAmphoraxe Life Sciences Inc.,Vancouver,BC V6L 3C9,CanadaCanada’s Michael Smith Genome Sciences Centre at BC Cancer,Vancouver,BC V5Z 4S6,CanadaDepartment of Biochemistry and Microbiology,University of Victoria,Victoria,BC V8P 5C2,CanadaBC Cancer,Vancouver,BC V5Z 1L3,CanadaCommunicable Disease Prevention and Response,British Columbia Centre for Disease Control,Vancouver,BC V6Z R4R,Canada School of Population and Public Health,University of British Columbia,Vancouver,BC V6T 1Z3,CanadaBritish Columbia Centre for Disease Control,Public Health Laboratory,Vancouver,BC V6Z R4R,Canada Department of Pathology and Laboratory Medicine,University of British Columbia,Vancouver,BC V6T 1Z4,CanadaDepartment of Chemistry,University of Victoria,Victoria,BC V8P 5C2,CanadaAmphoraxe Life Sciences Inc.,Vancouver,BC V6L 3C9,CanadaDepartment of Biochemistry and Microbiology,University of Victoria,Victoria,BC V8P 5C2,CanadaBritish Columbia Centre for Disease Control,Public Health Laboratory,Vancouver,BC V6Z R4R,Canada Genome Science and Technology Graduate Program,University of British Columbia,Vancouver,BC V6T 1Z4,Canada Canada’s Michael Smith Genome Sciences Centre at BC Cancer,Vancouver,BC V5Z 4S6,Canada Amphoraxe Life Sciences Inc.,Vancouver,BC V6L 3C9,Canada Department of Medical Genetics,University of British Columbia,Vancouver,BC V6T 1Z3,Canada
农业科技
Antimicrobial peptideAPECBroiler chickenEfficacyImmunomodulationSafetyTranscriptomics
《Journal of Animal Science and Biotechnology》 2026 (4)
P.2256-2272,17
provided by Chicken Farmers of Canada,Canadian Hatching Egg Producers,Investment Agriculture Foundation of British Columbia(INV106,INV247)Amphoraxe Life Sciences Inc.Partial support for trainees were provided by Mitacs(IT28945,IT43363)University of VictoriaUniversity of British ColumbiaAmphoraxe Life Sciences Inc。
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