{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:14:28Z","timestamp":1792044868168,"version":"4.4.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005019","name":"Beef Cattle Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012190","name":"Alberta Beef Producers","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Multidrug-resistant (MDR; resistance to \u22653 antimicrobial classes) members of the <jats:italic>Pasteurellaceae<\/jats:italic> family may compromise the efficacy of therapies used to prevent and treat bovine respiratory disease (BRD) in feedlot cattle. This study examined the prevalence of multidrug resistance in strains of <jats:italic>Mannheimia haemolytica<\/jats:italic> and <jats:italic>Pasteurella multocida<\/jats:italic> collected from BRD cattle mortalities in North America. Isolates of <jats:italic>M. haemolytica<\/jats:italic> (<jats:italic>n<\/jats:italic> = 147) and <jats:italic>P. multocida<\/jats:italic> (<jats:italic>n<\/jats:italic> = 70) spanning 69 Alberta feedlots from 2011 to 2016 and two United States feedlots from 2011 to 2012 were examined for antimicrobial resistance (AMR) in association with integrative and conjugative elements (ICEs). Overall, resistance was high in both bacterial species with an increase in the prevalence of MDR isolates between 2011 and 2016. Resistance to &amp;gt;7 antimicrobial drugs occurred in 31% of <jats:italic>M. haemolytica<\/jats:italic> and 83% of <jats:italic>P. multocida<\/jats:italic> isolates. Resistance to sulfadimethoxine, trimethoprim\/sulfamethoxazole, neomycin, clindamycin oxytetracycline, spectinomycin, tylosin, tilmicosin, and tulathromycin was most common. Although &amp;gt;80% of strains harbored three or more ICE-associated genes, only 12% of <jats:italic>M. haemolytica<\/jats:italic> and 77% of <jats:italic>P. multocida<\/jats:italic> contained all six, reflecting the diversity of ICEs. There was evidence of clonal spread as <jats:italic>P. multocida<\/jats:italic> and <jats:italic>M. haemolytica<\/jats:italic> isolates with the same pulsed-field gel electrophoresis profile from the United States in 2011 were isolated in Alberta in 2015\u20132016. This work highlights that MDR strains of <jats:italic>Pasteurellaceae<\/jats:italic> containing ICEs are widespread and may be contributing to BRD therapy failure in feedlot cattle. Given the antimicrobial resistance gene profiles identified, these MDR isolates may be selected for by the use of macrolides, tetracyclines, and\/or in-feed supplements containing heavy metals.<\/jats:p>","DOI":"10.3389\/fmicb.2020.606438","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T06:23:03Z","timestamp":1604557383000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":41,"title":["Multidrug Resistance in Pasteurellaceae Associated With Bovine Respiratory Disease Mortalities in North America From 2011 to 2016"],"prefix":"10.3389","volume":"11","author":[{"given":"Cassidy L.","family":"Klima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin B.","family":"Holman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun R.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheyenne C.","family":"Conrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda J.","family":"Ralston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Allan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Michele","family":"Anholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan D.","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Stanford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry J.","family":"Hannon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin W.","family":"Booker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim A.","family":"McAllister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2017.00207","article-title":"Antimicrobial susceptibility of bacteria that cause bovine respiratory disease complex in Alberta, Canada.","volume":"4","author":"Anholt","year":"2017","journal-title":"Front. Vet. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1128\/AAC.02522-13","article-title":"Class D \u03b2-lactamases: are they all carbapenemases?","volume":"58","author":"Antunes","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B3","first-page":"439","article-title":"Integrative conjugative elements (ICEs) of the SXT\/R391 group as vehicles for acquisition of resistance determinants, stable maintenance and transfer to a wide range of enterobacterial pathogens","author":"Armshaw","year":"2013","journal-title":"Microbial Pathogens and Strategies for Combating Them: Science, Technology and Education"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01329","article-title":"Integrative and conjugative elements (ICEs) in Pasteurellaceae species and their detection by multiplex PCR.","volume":"9","author":"Beker","year":"2018","journal-title":"Front. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2018.00153","article-title":"Integrative Conjugative Element ICEHs1 encodes for antimicrobial resistance and metal tolerance in Histophilus somni.","volume":"5","author":"Bhatt","year":"2018","journal-title":"Front. Vet. Sci."},{"key":"B6","first-page":"473","article-title":"Microbiological and histopathological findings in cases of fatal bovine respiratory disease of feedlot cattle in Western Canada.","volume":"49","author":"Booker","year":"2008","journal-title":"Can. Vet. J."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2019.00329","article-title":"Antimicrobial use on 36 beef feedlots in Western Canada: 2008-2012.","volume":"6","author":"Brault","year":"2019","journal-title":"Front. Vet. Sci."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00568-17","article-title":"A novel aadA aminoglycoside resistance gene in bovine and porcine pathogens.","volume":"3","author":"Cameron","year":"2018","journal-title":"mSphere"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01183","article-title":"Identification of a new antimicrobial resistance gene provides fresh insights into pleuromutilin resistance in Brachyspira hyodysenteriae, aetiological agent of swine dysentery.","volume":"9","author":"Card","year":"2018","journal-title":"Front. Microbiol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-016-3316-8","article-title":"Genomic signatures of Mannheimia haemolytica that associate with the lungs of cattle with respiratory disease, an integrative conjugative element, and antibiotic resistance genes.","volume":"17","author":"Clawson","year":"2016","journal-title":"BMC Genomics"},{"key":"B11","year":"2008","journal-title":"Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Collected From Animals; Approved Standard. CLSI Document M31-A3"},{"key":"B12","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1099\/jmm.0.05019-0","article-title":"Characterization and comparison of Pasteurella multocida strains associated with porcine pneumonia and atrophic rhinitis.","volume":"52","author":"Davies","year":"2003","journal-title":"J. Med. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"4128","DOI":"10.1128\/AAC.00450-11","article-title":"Combinations of macrolide resistance determinants in field isolates of Mannheimia haemolytica and Pasteurella multocida.","volume":"55","author":"Desmolaize","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B14","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1093\/jac\/dku361","article-title":"Analysis and comparative genomics of ICEMh1, a novel integrative and conjugative element (ICE) of Mannheimia haemolytica.","volume":"70","author":"Eidam","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"B15","year":"2009","journal-title":"Categorization of Antimicrobial Drugs Based on Importance in Human Medicine [Online]."},{"key":"B16","year":"2018","journal-title":"Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) 2016 annual report"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1128\/AAC.40.6.1558","article-title":"Distribution of tet(H) among Pasteurella isolates from the United States and Canada.","volume":"40","author":"Hansen","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1017\/S1466252314000115","article-title":"BRD in 2014: where have we been, where are we now, and where do we want to go?","volume":"15","author":"Hilton","year":"2014","journal-title":"Anim. Health Res. Rev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1146\/annurev-genet-112414-055018","article-title":"Integrative and conjugative elements (ICEs): what they do and how they work.","volume":"49","author":"Johnson","year":"2015","journal-title":"Annu. Rev. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1093\/jac\/dky515","article-title":"Plasmid-located extended-spectrum \u03b2-lactamase gene blaROB-2 in Mannheimia haemolytica.","volume":"74","author":"Kadlec","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"B21","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1093\/jac\/dki210","article-title":"tet(L)-mediated tetracycline resistance in bovine Mannheimia and Pasteurella isolates.","volume":"56","author":"Kehrenberg","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"B22","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1093\/jac\/48.5.631","article-title":"Tetracycline resistance genes in isolates of Pasteurella multocida, Mannheimia haemolytica, Mannheimia glucosida and Mannheimia varigena from bovine and swine respiratory disease: intergeneric spread of the tet(H) plasmid pMHT1.","volume":"48","author":"Kehrenberg","year":"2001","journal-title":"J. Antimicrob. Chemother."},{"key":"B23","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1128\/AAC.49.1.414-417.2005","article-title":"dfrA20, A novel trimethoprim resistance gene from Pasteurella multocida.","volume":"49","author":"Kehrenberg","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2244","DOI":"10.1128\/AAC.00229-07","article-title":"Mutations in 16S rRNA and ribosomal protein S5 associated with high-level spectinomycin resistance in Pasteurella multocida.","volume":"51","author":"Kehrenberg","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.vetmic.2010.11.018","article-title":"Genetic characterization and antimicrobial susceptibility of Mannheimia haemolytica isolated from the nasopharynx of feedlot cattle.","volume":"149","author":"Klima","year":"2011","journal-title":"Vet. Microbiol."},{"key":"B26","first-page":"38","article-title":"Characterization of Mannheimia haemolytica isolated from feedlot cattle that were healthy or treated for bovine respiratory disease.","volume":"78","author":"Klima","year":"","journal-title":"Can. J. Vet. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1128\/JCM.02485-13","article-title":"Pathogens of bovine respiratory disease in North American feedlots conferring multidrug resistance via integrative conjugative elements.","volume":"52","author":"Klima","year":"","journal-title":"J. Clin. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149520","article-title":"Comparative genomic analysis of Mannheimia haemolytica from bovine sources.","volume":"11","author":"Klima","year":"2016","journal-title":"PLoS One"},{"key":"B29","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1007\/s00248-019-01361-3","article-title":"Lower respiratory tract microbiome and resistome of bovine respiratory disease mortalities.","volume":"78","author":"Klima","year":"2019","journal-title":"Microb. Ecol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1177\/1040638712455634","article-title":"Occurrence of antimicrobial resistance and virulence genes, and distribution of enterococcal clonal complex 17 from animals and human beings in Korea.","volume":"24","author":"Kwon","year":"2012","journal-title":"J. Vet. Diagn. Invest."},{"key":"B31","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1177\/1040638713485227","article-title":"Antimicrobial multidrug resistance and coresistance patterns of Mannheimia haemolytica isolated from bovine respiratory disease cases\u2013a three-year (2009-2011) retrospective analysis.","volume":"25","author":"Lubbers","year":"2013","journal-title":"J. Vet. Diagn. Invest."},{"key":"B32","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1177\/1040638717737589","article-title":"Treatment history and antimicrobial susceptibility results for Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolates from bovine respiratory disease cases submitted to the Iowa State University Veterinary Diagnostic Laboratory from 2013 to 2015.","volume":"30","author":"Magstadt","year":"2018","journal-title":"J. Vet. Diagn. Invest."},{"key":"B33","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1093\/jac\/dkr406","article-title":"ICEPmu1, an integrative conjugative element (ICE) of Pasteurella multocida: analysis of the regions that comprise 12 antimicrobial resistance genes.","volume":"67","author":"Michael","year":"","journal-title":"J. Antimicrob. Chemother."},{"key":"B34","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1093\/jac\/dkr411","article-title":"ICEPmu1, an integrative conjugative element (ICE) of Pasteurella multocida: structure and transfer.","volume":"67","author":"Michael","year":"","journal-title":"J. Antimicrob. Chemother."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01298-16","article-title":"Carbapenemase-producing Enterobacteriaceae recovered from the environment of a swine farrow-to-finish operation in the United States.","volume":"61","author":"Mollenkopf","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"B36","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.vetmic.2019.01.016","article-title":"Plasmid-located dfrA14 gene in Pasteurella multocida isolates from three different pig-producing farms in Germany.","volume":"230","author":"Niemann","year":"2019","journal-title":"Vet. Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1093\/jac\/dku385","article-title":"Macrolide resistance conferred by rRNA mutations in field isolates of Mannheimia haemolytica and Pasteurella multocida.","volume":"70","author":"Olsen","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"B38","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.vetmic.2015.10.020","article-title":"Comparison of Mannheimia haemolytica isolates from an outbreak of bovine respiratory disease.","volume":"182","author":"Rainbolt","year":"2016","journal-title":"Vet. Microbiol."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-143","article-title":"MPprimer: a program for reliable multiplex PCR primer design.","volume":"11","author":"Shen","year":"2010","journal-title":"BMC Bioinform."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.2527\/jas.2016.1110","article-title":"Prevalence of multi drug antimicrobial resistance in isolated from high-risk stocker cattle at arrival and two weeks after processing.","volume":"95","author":"Snyder","year":"2017","journal-title":"J. Anim. Sci."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8020288","article-title":"Antimicrobial resistance in members of the bacterial bovine respiratory disease complex isolated from lung tissue of cattle mortalities managed with or without the use of antimicrobials.","volume":"8","author":"Stanford","year":"2020","journal-title":"Microorganisms"},{"key":"B42","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.vetmic.2017.07.01","article-title":"Prevalence and antimicrobial susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolated from the lower respiratory tract of healthy feedlot cattle and those diagnosed with bovine respiratory disease.","volume":"208","author":"Timsit","year":"2017","journal-title":"Vet. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.vetmic.2018.06.005","article-title":"Multidrug resistant Mannheimia haemolytica isolated from high-risk beef stocker cattle after antimicrobial metaphylaxis and treatment for bovine respiratory disease.","volume":"221","author":"Woolums","year":"2018","journal-title":"Vet. Microbiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1637\/z7035","article-title":"Molecular characterization of plasmids with antimicrobial resistant genes in avian isolates of Pasteurella multocida.","volume":"47","author":"Wu","year":"2003","journal-title":"Avian. Dis."}],"updated-by":[{"DOI":"10.3389\/fmicb.2020.638008","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000}}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2020.606438\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T21:24:08Z","timestamp":1612301048000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2020.606438\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,5]]},"references-count":44,"alternative-id":["10.3389\/fmicb.2020.606438"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2020.606438","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fmicb.2020.638008","asserted-by":"object"}]},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,5]]},"article-number":"606438"}}