{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:14:36Z","timestamp":1784646876940,"version":"3.55.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Innovation Fund of Denmark"},{"name":"Danish Poultry levy board"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Escherichia coli<\/jats:italic> constitutes an immense challenge to the poultry industry due to its devastating effect on productivity, mortality, and carcass condemnations. To aid future studies on disease mechanisms and interventions, an aerogenous infection model was established in adult broiler breeders. Hens (n\u2009=\u2009120) were randomly allocated into six groups receiving either aerosolised <jats:italic>E. coli<\/jats:italic> or vehicle, or intratracheal <jats:italic>E. coli<\/jats:italic> or vehicle. Replication of aerosol inoculation was performed on distinct days. Alternating euthanasia time points were predetermined in order to evaluate the progression of the disease. All animals were thoroughly necropsied, and bacteriological samples were collected as well as tissues for histopathology. Birds inoculated with <jats:italic>E. coli<\/jats:italic> exhibited clinical signs and developed characteristic gross and histopathological lesions of colibacillosis, including splenic fibrinoid necrosis, folliculitis, polyserositis and impaction of parabronchi with fibrinoheterophilic exudate and necrotic debris, as well as positive in situ localisation of intralesional <jats:italic>E. coli<\/jats:italic> by immunohistochemistry. This study presents a successful development of a discriminative colibacillosis model through aerosol inoculation of adult broiler breeders. Gross and histopathological lesions characteristic of colibacillosis were established in two independent experiments.<\/jats:p>","DOI":"10.1038\/s41598-021-98270-8","type":"journal-article","created":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T11:02:54Z","timestamp":1633086174000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Development of an aerogenous Escherichia coli infection model in adult broiler breeders"],"prefix":"10.1038","volume":"11","author":[{"given":"Sofie","family":"Kromann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke Heidemann","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders Miki","family":"Bojesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik Elvang","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Th\u00f8fner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,1]]},"reference":[{"key":"98270_CR1","first-page":"751","volume-title":"Colibacillosis","author":"LK Nolan","year":"2013","unstructured":"Nolan, L. K., Barnes, H. J., Vaillancourt, J.-P., Abdul-Aziz, T. & Logue, C. M. Colibacillosis 13th edn, 751\u2013805 (Wiley, 2013).","edition":"13"},{"key":"98270_CR2","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1080\/03079457.2015.1060584","volume":"44","author":"WJM Landman","year":"2015","unstructured":"Landman, W. J. M. & van Eck, J. H. H. The incidence and economic impact of the Escherichia coli peritonitis syndrome in Dutch poultry farming. Avian Pathol. 44, 370\u2013378. https:\/\/doi.org\/10.1080\/03079457.2015.1060584 (2015).","journal-title":"Avian Pathol."},{"key":"98270_CR3","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1136\/vr.151.12.355","volume":"151","author":"F Vandemaele","year":"2002","unstructured":"Vandemaele, F., Vereecken, M., Derijcke, J. & Goddeeris, B. M. Incidence and antibiotic resistance of pathogenic Escherichia coli among poultry in Belgium. Vet. Rec. 151, 355\u2013356. https:\/\/doi.org\/10.1136\/vr.151.12.355 (2002).","journal-title":"Vet. Rec."},{"key":"98270_CR4","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1136\/vr.137.9.215","volume":"137","author":"V Yogaratnam","year":"1995","unstructured":"Yogaratnam, V. Analysis of the causes of high-rates of carcass rejection at a poultry-processing plant. Vet. Rec. 137, 215\u2013217. https:\/\/doi.org\/10.1136\/vr.137.9.215 (1995).","journal-title":"Vet. Rec."},{"key":"98270_CR5","unstructured":"Gross, W. G. Diseases due to Escherichia coli in poultry. Escherichia coli in domestic animals and humans, 237\u2013259 (1994)."},{"key":"98270_CR6","first-page":"381","volume":"116","author":"C Ewers","year":"2003","unstructured":"Ewers, C., Janssen, T. & Wieler, L. H. Avian pathogenic Escherichia coli (APEC). Berl. Munch. Tierarztl. Wochenschr. 116, 381\u2013395 (2003).","journal-title":"Berl. Munch. Tierarztl. Wochenschr."},{"key":"98270_CR7","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1080\/03079450050118430","volume":"29","author":"A Zanella","year":"2000","unstructured":"Zanella, A. et al. Severe Escherichia coli O111 septicaemia and polyserositis in hens at the start of lay. Avian Pathol. 29, 311\u2013317. https:\/\/doi.org\/10.1080\/03079450050118430 (2000).","journal-title":"Avian Pathol."},{"key":"98270_CR8","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1637\/12006-113018-Reg.1","volume":"63","author":"ICN Thofner","year":"2019","unstructured":"Thofner, I. C. N. et al. Longitudinal study on causes of mortality in Danish broiler breeders. Avian Dis. 63, 400\u2013410 (2019).","journal-title":"Avian Dis."},{"key":"98270_CR9","doi-asserted-by":"publisher","DOI":"10.1080\/03079457.2020.1805411","author":"B Grafl","year":"2020","unstructured":"Grafl, B., GauSsmann, B., Sulejmanovic, T., Hess, C. & Hess, M. Risks and disease aetiologies of compromised performance in commercial broilers kept at lower stocking density and limited antimicrobial use. Avian Pathol. https:\/\/doi.org\/10.1080\/03079457.2020.1805411 (2020).","journal-title":"Avian Pathol."},{"key":"98270_CR10","first-page":"299","volume":"30","author":"M Dho-Moulin","year":"1999","unstructured":"Dho-Moulin, M. & Fairbrother, J. M. Avian pathogenic Escherichia coli (APEC). Vet. Res. 30, 299\u2013316 (1999).","journal-title":"Vet. Res."},{"key":"98270_CR11","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1128\/aem.01324-08","volume":"75","author":"C Ewers","year":"2009","unstructured":"Ewers, C., Antao, E.-M., Diehl, I., Philipp, H.-C. & Wieler, L. H. Intestine and environment of the chicken as reservoirs for extraintestinal pathogenic Escherichia coli strains with zoonotic potential. Appl. Environ. Microbiol. 75, 184\u2013192. https:\/\/doi.org\/10.1128\/aem.01324-08 (2009).","journal-title":"Appl. Environ. Microbiol."},{"key":"98270_CR12","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1080\/03079450802216652","volume":"37","author":"F Dziva","year":"2008","unstructured":"Dziva, F. & Stevens, M. P. Colibacillosis in poultry: Unravelling the molecular basis of virulence of avian pathogenic Escherichia coli in their natural hosts. Avian Pathol. 37, 355\u2013366. https:\/\/doi.org\/10.1080\/03079450802216652 (2008).","journal-title":"Avian Pathol."},{"key":"98270_CR13","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1080\/03079450500179046","volume":"34","author":"D Giovanardi","year":"2005","unstructured":"Giovanardi, D. et al. Avian pathogenic Escherichia coli transmission from broiler breeders to their progeny in an integrated poultry production chain. Avian Pathol. 34, 313\u2013318. https:\/\/doi.org\/10.1080\/03079450500179046 (2005).","journal-title":"Avian Pathol."},{"key":"98270_CR14","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.micpath.2008.08.005","volume":"45","author":"E-M Antao","year":"2008","unstructured":"Antao, E.-M. et al. The chicken as a natural model for extraintestinal infections caused by avian pathogenic Escherichia coli (APEC). Microb. Pathog. 45, 361\u2013369. https:\/\/doi.org\/10.1016\/j.micpath.2008.08.005 (2008).","journal-title":"Microb. Pathog."},{"key":"98270_CR15","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1080\/03079457.2013.775694","volume":"42","author":"WJM Landman","year":"2013","unstructured":"Landman, W. J. M., Heuvelink, A. & van Eck, J. H. H. Reproduction of the Escherichia coli peritonitis syndrome in laying hens. Avian Pathol. 42, 157\u2013162. https:\/\/doi.org\/10.1080\/03079457.2013.775694 (2013).","journal-title":"Avian Pathol."},{"key":"98270_CR16","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.vetmic.2014.02.043","volume":"170","author":"SE Pors","year":"2014","unstructured":"Pors, S. E., Olsen, R. H. & Christensen, J. P. Variations in virulence of avian pathogenic Escherichia coli demonstrated by the use of a new in vivo infection model. Vet. Microbiol. 170, 368\u2013374. https:\/\/doi.org\/10.1016\/j.vetmic.2014.02.043 (2014).","journal-title":"Vet. Microbiol."},{"key":"98270_CR17","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3382\/ps\/pev320","volume":"95","author":"RF Wideman","year":"2016","unstructured":"Wideman, R. F. Bacterial chondronecrosis with osteomyelitis and lameness in broilers: A review. Poult. Sci. 95, 325\u2013344. https:\/\/doi.org\/10.3382\/ps\/pev320 (2016).","journal-title":"Poult. Sci."},{"key":"98270_CR18","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1637\/7176-030404r","volume":"48","author":"PS Gibbs","year":"2004","unstructured":"Gibbs, P. S., Petermann, S. R. & Wooley, R. E. Comparison of several challenge models for studies in avian colibacillosis. Avian Dis. 48, 751\u2013758. https:\/\/doi.org\/10.1637\/7176-030404r (2004).","journal-title":"Avian Dis."},{"key":"98270_CR19","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1080\/03079459808419375","volume":"27","author":"CA Ginns","year":"1998","unstructured":"Ginns, C. A., Browning, G. F., Benham, M. L. & Whithear, K. G. Development and application of an aerosol challenge method for reproduction of avian colibacillosis. Avian Pathol. 27, 505\u2013511. https:\/\/doi.org\/10.1080\/03079459808419375 (1998).","journal-title":"Avian Pathol."},{"key":"98270_CR20","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1128\/jb.188.3.977-987.2006","volume":"188","author":"I Chouikha","year":"2006","unstructured":"Chouikha, I. et al. A selC-associated genomic island of the extraintestinal avian pathogenic Escherichia coli strain BEN2908 is involved in carbohydrate uptake and virulence. J. Bacteriol. 188, 977\u2013987. https:\/\/doi.org\/10.1128\/jb.188.3.977-987.2006 (2006).","journal-title":"J. Bacteriol."},{"key":"98270_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1637\/10536-032213-Reg.1","volume":"58","author":"AA Chaudhari","year":"2014","unstructured":"Chaudhari, A. A. & Kariyawasam, S. An experimental infection model for Escherichia coli egg peritonitis in layer chickens. Avian Dis. 58, 25\u201333. https:\/\/doi.org\/10.1637\/10536-032213-Reg.1 (2014).","journal-title":"Avian Dis."},{"key":"98270_CR22","volume-title":"Handbook of Laboratory Animal Science","author":"J Hau","year":"2011","unstructured":"Hau, J. & Schapiro, S. J. Handbook of Laboratory Animal Science 3rd edn. (CRC Taylor & Francis distributor, 2011).","edition":"3"},{"key":"98270_CR23","unstructured":"Jensen, H. E. Animal models in mycology in Handbook of Laboratory Animal Science Vol. II (ed Hau J. and Schapiro S. J.) Ch. 15, (CRC Taylor & Francis distributor, 2011)."},{"key":"98270_CR24","unstructured":"Festing, M. F. W., Overend, P., Gaines Das, R., Cortina Borja, M., Berdoy, M. The Design of Animal Experiments: Reducing the Use of Animals in Research Through Better Experimental Design\u00a02nd edn, (SAGE Publications Ltd, 2016)."},{"key":"98270_CR25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007824","author":"C Kilkenny","year":"2009","unstructured":"Kilkenny, C. et al. Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PLoS ONE https:\/\/doi.org\/10.1371\/journal.pone.0007824 (2009).","journal-title":"PLoS ONE"},{"key":"98270_CR26","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/0742-8413(85)90021-0","volume":"81","author":"M Gleeson","year":"1985","unstructured":"Gleeson, M., Haigh, A. L., Molony, V. & Anderson, L. S. Ventilatory and cardiovascular-responses of the unanesthetized chicken, gallus-domesticus, to the respiratory stimulants etamiphylline and almitrine. Comp. Biochem. Physiol. C-Toxicol. Pharmacol. 81, 367\u2013374. https:\/\/doi.org\/10.1016\/0742-8413(85)90021-0 (1985).","journal-title":"Comp. Biochem. Physiol. C-Toxicol. Pharmacol."},{"key":"98270_CR27","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1046\/j.1472-765X.1998.00445.x","volume":"27","author":"J Chen","year":"1998","unstructured":"Chen, J. & Griffiths, M. W. PCR differentiation of Escherichia coli from other Gram-negative bacteria using primers derived from the nucleotide sequences flanking the gene encoding the universal stress protein. Lett. Appl. Microbiol. 27, 369\u2013371. https:\/\/doi.org\/10.1046\/j.1472-765X.1998.00445.x (1998).","journal-title":"Lett. Appl. Microbiol."},{"key":"98270_CR28","doi-asserted-by":"publisher","DOI":"10.1128\/aem.02812-18","author":"F Camelena","year":"2019","unstructured":"Camelena, F. et al. Rapid and simple universal Escherichia coli genotyping method based on multiple-locus variable-number tandem-repeat analysis using single-tube multiplex PCR and standard gel electrophoresis. Appl. Environ. Microbiol. https:\/\/doi.org\/10.1128\/aem.02812-18 (2019).","journal-title":"Appl. Environ. Microbiol."},{"key":"98270_CR29","unstructured":"Bancroft, J. D., Stevens, A. and Dawswon, M. P. The haematoxylins and eosin in Theory and Practice of Histological Techniques. (ed Wilson I.G. Stevens A.) pp. 99\u2013112. (Churchill Livingstone, 1996)."},{"key":"98270_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/1751-0147-52-48","author":"LK Isling","year":"2010","unstructured":"Isling, L. K., Aalbaek, B., Schroder, M. & Leifsson, P. S. Pyelonephritis in slaughter pigs and sows: Morphological characterization and aspects of pathogenesis and aetiology. Acta Vet. Scand. https:\/\/doi.org\/10.1186\/1751-0147-52-48 (2010).","journal-title":"Acta Vet. Scand."},{"key":"98270_CR31","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.2147\/cia.s183344","volume":"13","author":"TJ Bowerman","year":"2018","unstructured":"Bowerman, T. J., Zhang, J. & Waite, L. M. Antibacterial treatment of aspiration pneumonia in older people: a systematic review. Clin. Interv. Aging 13, 2201\u20132213. https:\/\/doi.org\/10.2147\/cia.s183344 (2018).","journal-title":"Clin. Interv. Aging"},{"key":"98270_CR32","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1097\/00003246-200112000-00001","volume":"29","author":"JA Rebuck","year":"2001","unstructured":"Rebuck, J. A., Rasmussen, J. R. & Olsen, K. M. Clinical aspiration-related practice patterns in the intensive care unit: A physician survey. Crit. Care Med. 29, 2239\u20132244. https:\/\/doi.org\/10.1097\/00003246-200112000-00001 (2001).","journal-title":"Crit. Care Med."},{"key":"98270_CR33","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1093\/ps\/84.4.553","volume":"84","author":"AJ Mireles","year":"2005","unstructured":"Mireles, A. J., Kim, S. A. & Klasing, K. C. An acute inflammatory response alters bone homeostasis, body composition, and the humoral immune response of broiler chickens. Poult. Sci. 84, 553\u2013560. https:\/\/doi.org\/10.1093\/ps\/84.4.553 (2005).","journal-title":"Poult. Sci."},{"key":"98270_CR34","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1093\/ps\/82.7.1108","volume":"82","author":"WE Huff","year":"2003","unstructured":"Huff, W. E., Huff, G. R., Rath, N. C., Balog, J. M. & Donoghue, A. M. Evaluation of aerosol spray and intramuscular injection of bacteriophage to treat an Escherichia coli respiratory infection. Poult. Sci. 82, 1108\u20131112. https:\/\/doi.org\/10.1093\/ps\/82.7.1108 (2003).","journal-title":"Poult. Sci."},{"key":"98270_CR35","doi-asserted-by":"publisher","first-page":"281","DOI":"10.2478\/s13382-012-0032-8","volume":"25","author":"K Brodka","year":"2012","unstructured":"Brodka, K., Kozajda, A., Buczynska, A. & Szadkowska-Stanczyk, I. The variability of bacterial aerosol in poultry houses depending on selected factors. Int. J. Occup. Med. Environ. Health 25, 281\u2013293. https:\/\/doi.org\/10.2478\/s13382-012-0032-8 (2012).","journal-title":"Int. J. Occup. Med. Environ. Health"},{"key":"98270_CR36","doi-asserted-by":"crossref","unstructured":"Nolan, L. K., Barnes, H. J., Vaillancourt, J.-P. & Abdul-Aziz, T. L., Catherine M. Colibacillosis in Diseases of Poultry (ed David E. Swayne) Ch. 18, 751\u2013805. (2013).","DOI":"10.1002\/9781119421481.ch18"},{"key":"98270_CR37","doi-asserted-by":"publisher","first-page":"7417","DOI":"10.1128\/aem.01380-09","volume":"75","author":"HN Chinivasagam","year":"2009","unstructured":"Chinivasagam, H. N., Tran, T., Maddock, L., Gale, A. & Blackall, P. J. Mechanically ventilated broiler sheds: A possible source of aerosolized Salmonella, Campylobacter, and Escherichia coli. Appl. Environ. Microbiol. 75, 7417\u20137425. https:\/\/doi.org\/10.1128\/aem.01380-09 (2009).","journal-title":"Appl. Environ. Microbiol."},{"key":"98270_CR38","doi-asserted-by":"publisher","first-page":"297","DOI":"10.2307\/1588229","volume":"12","author":"HC Carlson","year":"1968","unstructured":"Carlson, H. C. & Whenham, G. R. Coliform bacteria in chicken broiler house dust and their possible relationship to coli-septicemia. Avian Dis. 12, 297\u2013300. https:\/\/doi.org\/10.2307\/1588229 (1968).","journal-title":"Avian Dis."},{"key":"98270_CR39","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/0300-9629(86)90575-x","volume":"83","author":"M Gleeson","year":"1986","unstructured":"Gleeson, M. Respiratory adjustments of the unanesthetized chicken, gallus-domesticus, to elevated metabolism elicited by 2,4-dinitrophenol or cold-exposure. Comp. Biochem. Physiol. Physiol. 83, 283\u2013289. https:\/\/doi.org\/10.1016\/0300-9629(86)90575-x (1986).","journal-title":"Comp. Biochem. Physiol. Physiol."},{"key":"98270_CR40","doi-asserted-by":"publisher","first-page":"356","DOI":"10.3390\/ani3020356","volume":"3","author":"LJ Lara","year":"2013","unstructured":"Lara, L. J. & Rostagno, M. H. Impact of heat stress on poultry production. Animals Open Access J. MDPI 3, 356\u2013369. https:\/\/doi.org\/10.3390\/ani3020356 (2013).","journal-title":"Animals Open Access J. MDPI"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-98270-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-98270-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-98270-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T16:14:48Z","timestamp":1670084088000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-98270-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["98270"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-98270-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]},"assertion":[{"value":"18 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19556"}}