{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:41:54Z","timestamp":1792791714747,"version":"4.5.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"33","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"RDAR","award":["2021R003R"],"award-info":[{"award-number":["2021R003R"]}],"id":[{"id":"https:\/\/ror.org\/0537mjm80","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,8,13]]},"abstract":"<jats:p>\n                    Johne\u2019s disease (JD), a chronic, infectious enteritis caused by\n                    <jats:italic>Mycobacterium avium<\/jats:italic>\n                    subsp.\n                    <jats:italic>paratuberculosis<\/jats:italic>\n                    (MAP), affects wild and domestic ruminants. There is no cure or effective prevention, and current vaccines have substantial limitations, leaving this disease widespread in all substantial dairy industries causing economic, and animal welfare implications. Mycobacteriophages (MPs) have been gaining interest in recent years and are proposed as a promising solution to curtailing MAP infection. Using a well-validated infection model, we have demonstrated the preventative potential of MPs to protect dairy calves against MAP infection. Calves were supplemented daily with a phage cocktail from birth till weaning at 2 m of age and inoculated with MAP at 2 wk of age. Infection status was measured for 4.5 mo through blood, fecal, and postmortem tissue samples. Our findings highlight the remarkable efficacy of orally administered MPs. Notably, fecal shedding of MAP was entirely eliminated within 10 wk, in contrast to the infected control group where shedding continued for the entirety of the trial period. Postmortem tissue culture analysis further supported the effectiveness of MPs, with only 1 out of 6 animals in the phage-treated group testing positive for MAP colonized tissues compared to 6 out of 6 animals in the infected control group. Additionally, plaque assay results demonstrated the ability of phages to persist within the intestinal tract. Collectively, these results underscore the potential of orally administered MP cocktails as a highly effective intervention strategy to combat JD in dairy calves and by extension in the dairy industry.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2318627121","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T15:05:17Z","timestamp":1722870317000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["Lining the small intestine with mycobacteriophages protects from\n                    <i>Mycobacterium avium<\/i>\n                    subsp.\n                    <i>paratuberculosis<\/i>\n                    and eliminates fecal shedding"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0983-4558","authenticated-orcid":false,"given":"Victoria K.","family":"Harman-McKenna","sequence":"first","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5843-0727","authenticated-orcid":false,"given":"Razieh","family":"Eshraghisamani","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6534-4879","authenticated-orcid":false,"given":"Natali","family":"Shafer","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4824-9580","authenticated-orcid":false,"given":"Jeroen","family":"De Buck","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"e_1_3_4_1_2","volume-title":": Organism, disease, control","author":"Behr M. A.","year":"2020","unstructured":"M. A. Behr, K. Stevenson, V. Kapur, : Organism, disease, control (CABI, 2020)."},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-51328-0"},{"key":"e_1_3_4_3_2","first-page":"569","article-title":"Estimate of the direct production losses in Canadian dairy herds with subclinical Mycobacterium avium subspecies paratuberculosis infection","volume":"49","author":"Tiwari A.","year":"2008","unstructured":"A. Tiwari, J. A. VanLeeuwen, I. R. Dohoo, G. P. Keefe, A. Weersink, Estimate of the direct production losses in Canadian dairy herds with subclinical Mycobacterium avium subspecies paratuberculosis infection. Can. Vet. J. 49, 569\u2013576 (2008).","journal-title":"Can. Vet. J."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1017\/S095026881500076X"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/tbed.12723"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01372.x"},{"key":"e_1_3_4_7_2","first-page":"169","article-title":"A systematic review of risk factors associated with the introduction of Mycobacterium avium spp. paratuberculosis (MAP) into dairy herds","volume":"56","author":"Rangel S. J.","year":"2015","unstructured":"S. J. Rangel , A systematic review of risk factors associated with the introduction of Mycobacterium avium spp. paratuberculosis (MAP) into dairy herds. Can. Vet. J. 56, 169\u2013177 (2015).","journal-title":"Can. Vet. J."},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2014-9241"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022-0302(98)75577-8"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2007.12.011"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8091427"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2009-2860"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/inp.k952"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-015-0192-1"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.4292\/wjgpt.v8.i3.162"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1017\/S146625232300004X"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2006.12.1"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-44-94"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2011.02.026"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2002.tb11142.x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2007.05.002"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-765X.2004.01525.x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11010001"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1051\/rnd:19850401"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305923110"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2017.04.018"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2020.108665"},{"key":"e_1_3_4_28_2","unstructured":"A. G\u00f3rski \u201cChapter 2\u2013Phage as a modulator of immune responses: Practical implications for phage therapy\u201d in Bacteriophages Part B M. \u0141obocka W. Szybalski Eds. (Advances in Virus Research Academic Press UK 2012) vol. 83 pp. 41\u201371."},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2014.08.007"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-015-0185-0"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2017-13544"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.applanim.2015.11.011"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/v16010020"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-42-117"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2007.03.009"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2017.02.017"},{"key":"e_1_3_4_37_2","volume-title":"Diagnosis and Control of Johne\u2019s Disease","author":"National Research Council","year":"2003","unstructured":"National Research Council, Diagnosis and Control of Johne\u2019s Disease (The National Academies Press US, Washington, DC, 2003), vol. 3."},{"key":"e_1_3_4_38_2","first-page":"453","article-title":"Interpretation of the gamma interferon test for diagnosis of subclinical paratuberculosis in cattle","volume":"9","author":"Jungersen G.","year":"2002","unstructured":"G. Jungersen, A. Huda, J. J. Hansen, P. Lind, Interpretation of the gamma interferon test for diagnosis of subclinical paratuberculosis in cattle. Clin. Diagn. Lab. Immunol. 9, 453\u2013460 (2002).","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00995-13"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2005.04.002"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.4.6.368"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijfoodmicro.2008.08.013"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2013.10.040"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2013.00288"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.2012.0021"},{"key":"e_1_3_4_47_2","unstructured":"Geneious Prime Version 2024.0.4. https:\/\/www.geneious.com. Accessed 14 April 2024."},{"key":"e_1_3_4_48_2","unstructured":"Posit team RStudio: Integrated Development Environment for R (Version 2022.02.3+492 Posit Software PBC Boston MA 2023)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2318627121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T15:07:24Z","timestamp":1722870444000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2318627121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,5]]},"references-count":48,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2024,8,13]]}},"alternative-id":["10.1073\/pnas.2318627121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2318627121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,5]]},"assertion":[{"value":"2023-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2318627121"}}