{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:27:07Z","timestamp":1791822427469,"version":"4.3.4"},"reference-count":70,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010576","name":"Iowa Pork Producers Association","doi-asserted-by":"publisher","award":["NPB #16-113"],"award-info":[{"award-number":["NPB #16-113"]}],"id":[{"id":"10.13039\/100010576","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Multidrug-resistant (MDR; resistance to &gt;3 antimicrobial classes) Salmonella enterica serovar I 4,[5],12:i:- strains were linked to a 2015 foodborne outbreak from pork. Strain USDA15WA-1, associated with the outbreak, harbors an MDR module and the metal tolerance element Salmonella Genomic Island 4 (SGI-4). Characterization of SGI-4 revealed that conjugational transfer of SGI-4 resulted in the mobile genetic element (MGE) replicating as a plasmid or integrating into the chromosome. Tolerance to copper, arsenic, and antimony compounds was increased in Salmonella strains containing SGI-4 compared to strains lacking the MGE. Following Salmonella exposure to copper, RNA-seq transcriptional analysis demonstrated significant differential expression of diverse genes and pathways, including induction of at least 38 metal tolerance genes (copper, arsenic, silver, and mercury). Evaluation of swine administered elevated concentrations of zinc oxide (2000 mg\/kg) and copper sulfate (200 mg\/kg) as an antimicrobial feed additive (Zn+Cu) in their diet for four weeks prior to and three weeks post-inoculation with serovar I 4,[5],12:i:- indicated that Salmonella shedding levels declined at a slower rate in pigs receiving in-feed Zn+Cu compared to control pigs (no Zn+Cu). The presence of metal tolerance genes in MDR Salmonella serovar I 4,[5],12:i:- may provide benefits for environmental survival or swine colonization in metal-containing settings.<\/jats:p>","DOI":"10.3390\/genes11111291","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:21:06Z","timestamp":1604017266000},"page":"1291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The Role of Salmonella Genomic Island 4 in Metal Tolerance of Salmonella enterica Serovar I 4,[5],12:i:- Pork Outbreak Isolate USDA15WA-1"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-7424","authenticated-orcid":false,"given":"Bradley L.","family":"Bearson","sequence":"first","affiliation":[{"name":"USDA, ARS, National Laboratory for Agriculture and the Environment, Agroecosystems Management Research Unit, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian M.","family":"Trachsel","sequence":"additional","affiliation":[{"name":"USDA, ARS, National Animal Disease Center, Food Safety and Enteric Pathogens, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Shippy","sequence":"additional","affiliation":[{"name":"USDA, ARS, National Animal Disease Center, Food Safety and Enteric Pathogens, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathesh K.","family":"Sivasankaran","sequence":"additional","affiliation":[{"name":"USDA, ARS, National Animal Disease Center, Food Safety and Enteric Pathogens, Ames, IA 50010, USA"},{"name":"Genome Informatics Facility, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Kerr","sequence":"additional","affiliation":[{"name":"USDA, ARS, National Laboratory for Agriculture and the Environment, Agroecosystems Management Research Unit, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2996-0334","authenticated-orcid":false,"given":"Crystal L.","family":"Loving","sequence":"additional","affiliation":[{"name":"USDA, ARS, National Animal Disease Center, Food Safety and Enteric Pathogens, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W.","family":"Brunelle","sequence":"additional","affiliation":[{"name":"USDA, ARS, National Animal Disease Center, Food Safety and Enteric Pathogens, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9842-368X","authenticated-orcid":false,"given":"Shelby M.","family":"Curry","sequence":"additional","affiliation":[{"name":"USDA, ARS, National Laboratory for Agriculture and the Environment, Agroecosystems Management Research Unit, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7283-4782","authenticated-orcid":false,"given":"Nicholas K.","family":"Gabler","sequence":"additional","affiliation":[{"name":"Animal Science Department, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn M. D.","family":"Bearson","sequence":"additional","affiliation":[{"name":"USDA, ARS, National Animal Disease Center, Food Safety and Enteric Pathogens, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"key":"ref_1","unstructured":"CDC (2020, May 12). Salmonella, Available online: https:\/\/www.cdc.gov\/salmonella\/index.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetmic.2007.12.017","article-title":"Non-typhoidal Salmonella infections in pigs: A closer look at epidemiology, pathogenesis and control","volume":"130","author":"Boyen","year":"2008","journal-title":"Vet. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.aninu.2018.04.006","article-title":"Animals as sources of food-borne pathogens: A review","volume":"4","author":"Heredia","year":"2018","journal-title":"Anim. Nutr."},{"key":"ref_4","unstructured":"CDC (2020, May 12). National Outbreak Reporting System Dashboard, Available online: https:\/\/wwwn.cdc.gov\/norsdashboard\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"379","DOI":"10.15585\/mmwr.mm6514a4","article-title":"Notes from the Field: Outbreak of Multidrug-Resistant Salmonella Infections Linked to Pork--Washington, 2015","volume":"65","author":"Kawakami","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00791-19","DOI":"10.1128\/MRA.00791-19","article-title":"Complete Genome Sequence of Multidrug-Resistant Salmonella enterica Serovar I 4,[5],12:i:- 2015 U.S. Pork Outbreak Isolate USDA15WA-1","volume":"8","author":"Bearson","year":"2019","journal-title":"Microbiol. Resour. Announc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3389\/fmicb.2018.00715","article-title":"A Comparative Genomic Analysis Provides Novel Insights Into the Ecological Success of the Monophasic Salmonella Serovar 4,[5],12:i","volume":"9","author":"Mastrorilli","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1089\/fpd.2008.0213","article-title":"Emergence, distribution, and molecular and phenotypic characteristics of Salmonella enterica serotype 4,5,12:i","volume":"6","author":"Switt","year":"2009","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_9","unstructured":"CDC (2018). National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS): Human Isolates Surveillance Report for 2015 (Final Report)."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"680","DOI":"10.3389\/fmicb.2016.00680","article-title":"Horizontal Acquisition of a Multidrug-Resistance Module (R-type ASSuT) Is Responsible for the Monophasic Phenotype in a Widespread Clone of Salmonella Serovar 4,[5],12:i","volume":"7","author":"Garcia","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"617","DOI":"10.3201\/eid2204.150531","article-title":"Microevolution of Monophasic Salmonella Typhimurium during Epidemic, United Kingdom, 2005\u20132010","volume":"22","author":"Petrovska","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e01758-17","DOI":"10.1128\/JCM.01758-17","article-title":"Phylogenetic Characterization of Salmonella enterica Serovar Typhimurium and Its Monophasic Variant Isolated from Food Animals in Japan Revealed Replacement of Major Epidemic Clones in the Last 4 Decades","volume":"56","author":"Arai","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.ijantimicag.2015.01.013","article-title":"Metal tolerance in emerging clinically relevant multidrug-resistant Salmonella enterica serotype 4,[5],12:i:- clones circulating in Europe","volume":"45","author":"Mourao","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1128\/AEM.04283-13","article-title":"In-feed use of heavy metal micronutrients in U.S. swine production systems and its role in persistence of multidrug-resistant Salmonellae","volume":"80","author":"Medardus","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.micinf.2008.04.011","article-title":"Iron regulated genes of Salmonella enterica serovar Typhimurium in response to norepinephrine and the requirement of fepDGC for norepinephrine-enhanced growth","volume":"10","author":"Bearson","year":"2008","journal-title":"Microbes Infect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.mimet.2008.06.010","article-title":"Antibiotic marker modifications of lambda Red and FLP helper plasmids, pKD46 and pCP20, for inactivation of chromosomal genes using PCR products in multidrug-resistant strains","volume":"75","author":"Doublet","year":"2008","journal-title":"J. Microbiol. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1089\/fpd.2017.2378","article-title":"Porcine Response to a Multidrug-Resistant Salmonella enterica serovar I 4,[5],12:i:- Outbreak Isolate","volume":"15","author":"Shippy","year":"2018","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1128\/AEM.72.4.2829-2836.2006","article-title":"Identification of Salmonella enterica serovar Typhimurium genes important for survival in the swine gastric environment","volume":"72","author":"Bearson","year":"2006","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_19","unstructured":"Bushnell, B. (2020, October 27). BBMap. Available online: https:\/\/sourceforge.net\/projects\/bbmap\/."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wick, R.R., Judd, L.M., Gorrie, C.L., and Holt, K.E. (2017). Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005595"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., and Madden, T.L. (2009). BLAST+: Architecture and applications. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-421"},{"key":"ref_22","unstructured":"Team, R.C (2020, August 07). R: A Language and Environment for Statistical Computing. Available online: https:\/\/www.r-project.org\/."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1093\/bioinformatics\/btt291","article-title":"opm: An R package for analysing OmniLog((R)) phenotype microarray data","volume":"29","author":"Vaas","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hoffmann, S., Otto, C., Kurtz, S., Sharma, C.M., Khaitovich, P., Vogel, J., Stadler, P.F., and Hackermuller, J. (2009). Fast mapping of short sequences with mismatches, insertions and deletions using index structures. PLoS Comput. Biol., 5.","DOI":"10.1371\/journal.pcbi.1000502"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gene Ontology Consortium (2019). The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res., 47, D330\u2013D338.","DOI":"10.1093\/nar\/gky1055"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1093\/bioinformatics\/btu031","article-title":"InterProScan 5: Genome-scale protein function classification","volume":"30","author":"Jones","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_29","unstructured":"Alexa, A., and Rahnenfuhrer, J. (2020, October 27). topGO: Enrichment Analysis for Gene Ontology; R Package Version 2.40.0. Available online: https:\/\/rdrr.io\/bioc\/topGO\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.micpath.2010.03.005","article-title":"The Salmonella enterica serovar Typhimurium QseB response regulator negatively regulates bacterial motility and swine colonization in the absence of the QseC sensor kinase","volume":"48","author":"Bearson","year":"2010","journal-title":"Microb. Pathog."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3389\/fvets.2016.00066","article-title":"Prophylactic Administration of Vector-Encoded Porcine Granulocyte-Colony Stimulating Factor Reduces Salmonella Shedding, Tonsil Colonization, and Microbiota Alterations of the Gastrointestinal Tract in Salmonella-Challenged Swine","volume":"3","author":"Bearson","year":"2016","journal-title":"Front. Vet. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J. Stat. Softw."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"26","DOI":"10.18637\/jss.v082.i13","article-title":"lmerTest Package: Tests in Linear Mixed Effects Models","volume":"82","author":"Kuznetsova","year":"2017","journal-title":"J. Stat. Softw."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.3389\/fimmu.2019.01381","article-title":"Dietary Resistant Potato Starch Alters Intestinal Microbial Communities and Their Metabolites, and Markers of Immune Regulation and Barrier Function in Swine","volume":"10","author":"Trachsel","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1128\/AEM.01541-09","article-title":"Introducing mothur: Open-source, platform-independent, community-supported software for describing and comparing microbial communities","volume":"75","author":"Schloss","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_36","unstructured":"Oksanen, J., Blanchet, F.G., Friendly, M., Kindt, R., Legendre, P., McGlinn, D., Minchin, P.R., O\u2019Hara, R.B., Simpson, G.L., and Solymos, P. (2020, October 27). vegan: Community Ecology Package, 2.5.6. Available online: https:\/\/rdrr.io\/cran\/vegan\/."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"McMurdie, P.J., and Holmes, S. (2013). phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census Data. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061217"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.3389\/fmicb.2019.01118","article-title":"SGI-4 in Monophasic Salmonella Typhimurium ST34 Is a Novel ICE That Enhances Resistance to Copper","volume":"10","author":"Branchu","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e00429-19","DOI":"10.1128\/AAC.00429-19","article-title":"Salmonella Genomic Island 3 Is an Integrative and Conjugative Element and Contributes to Copper and Arsenic Tolerance of Salmonella enterica","volume":"63","author":"Arai","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chalmers, G., Rozas, K.M., Amachawadi, R.G., Scott, H.M., Norman, K.N., Nagaraja, T.G., Tokach, M.D., and Boerlin, P. (2018). Distribution of the pco Gene Cluster and Associated Genetic Determinants among Swine Escherichia coli from a Controlled Feeding Trial. Genes, 9.","DOI":"10.3390\/genes9100504"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/B978-0-12-381043-4.00005-2","article-title":"Metal sensing in Salmonella: Implications for pathogenesis","volume":"58","author":"Osman","year":"2011","journal-title":"Adv. Microb. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8344","DOI":"10.1073\/pnas.0812808106","article-title":"The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity","volume":"106","author":"Macomber","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jinorgbio.2012.04.009","article-title":"PcoE\u2014A metal sponge expressed to the periplasm of copper resistance Escherichia coli. Implication of its function role in copper resistance","volume":"115","author":"Zimmermann","year":"2012","journal-title":"J. Inorg. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1099\/mic.0.080473-0","article-title":"Identification of a Salmonella ancillary copper detoxification mechanism by a comparative analysis of the genome-wide transcriptional response to copper and zinc excess","volume":"160","author":"Pontel","year":"2014","journal-title":"Microbiology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e00126-18","DOI":"10.1128\/JB.00126-18","article-title":"CpxR\/CpxA Controls scsABCD Transcription to Counteract Copper and Oxidative Stress in Salmonella enterica Serovar Typhimurium","volume":"200","author":"Lopez","year":"2018","journal-title":"J. Bacteriol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11573","DOI":"10.1073\/pnas.1603192113","article-title":"Compartment and signal-specific codependence in the transcriptional control of Salmonella periplasmic copper homeostasis","volume":"113","author":"Pezza","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.2527\/1993.71113020x","article-title":"Growth and plasma zinc responses of young pigs fed pharmacologic levels of zinc","volume":"71","author":"Hahn","year":"1993","journal-title":"J. Anim. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s12011-012-9422-9","article-title":"Zinc oxide-montmorillonite hybrid influences diarrhea, intestinal mucosal integrity, and digestive enzyme activity in weaned pigs","volume":"149","author":"Hu","year":"2012","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.2527\/2002.8071917x","article-title":"Effect of feeding organic and inorganic sources of additional zinc on growth performance and zinc balance in nursery pigs","volume":"80","author":"Case","year":"2002","journal-title":"J. Anim. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jtemb.2018.01.006","article-title":"Influence of zinc supplementation on immune parameters in weaned pigs","volume":"49","author":"Kloubert","year":"2018","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/j.1439-0396.2011.01231.x","article-title":"Dose-dependent effects of dietary zinc oxide on bacterial communities and metabolic profiles in the ileum of weaned pigs","volume":"96","author":"Pieper","year":"2012","journal-title":"J. Anim. Physiol. Anim. Nutr. (Berl.)"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"94","DOI":"10.2527\/jas.2005-686","article-title":"Use of mannanoligosaccharides and zinc chelate as growth promoters and diarrhea preventative in weaning pigs: Effects on microbiota and gut function","volume":"86","author":"Castillo","year":"2008","journal-title":"J. Anim. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Liu, P., Pieper, R., Rieger, J., Vahjen, W., Davin, R., Plendl, J., Meyer, W., and Zentek, J. (2014). Effect of dietary zinc oxide on morphological characteristics, mucin composition and gene expression in the colon of weaned piglets. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091091"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1017\/S0007114509289033","article-title":"Supplemental zinc reduced intestinal permeability by enhancing occludin and zonula occludens protein-1 (ZO-1) expression in weaning piglets","volume":"102","author":"Zhang","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1128\/AEM.71.5.2267-2277.2005","article-title":"Influence of dietary zinc oxide and copper sulfate on the gastrointestinal ecosystem in newly weaned piglets","volume":"71","author":"Hojberg","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.2527\/jas.2006-434","article-title":"Growth performance and intestinal morphology responses in early weaned pigs to supplementation of antibiotic-free diets with an organic copper complex and spray-dried plasma protein in sanitary and nonsanitary environments","volume":"85","author":"Zhao","year":"2007","journal-title":"J. Anim. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.2527\/jas1981.5161347x","article-title":"Effects of the dietary inclusion of copper and(or) antibiotics on the performance of weanling pigs","volume":"51","author":"Stahly","year":"1980","journal-title":"J. Anim. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"414","DOI":"10.2527\/jas.2010-2839","article-title":"Additivity of effects from dietary copper and zinc on growth performance and fecal microbiota of pigs after weaning","volume":"89","author":"Perez","year":"2011","journal-title":"J. Anim. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"511","DOI":"10.4141\/A05-075","article-title":"Effect of pharmacological intakes of zinc and copper on growth performance, circulating cytokines and gut microbiota of newly weaned piglets challenged with coliform lipopolysaccharides","volume":"86","author":"Namkung","year":"2006","journal-title":"Can. J. Anim. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1093\/jac\/dkw120","article-title":"Tolerance to multiple metal stressors in emerging non-typhoidal MDR Salmonella serotypes: A relevant role for copper in anaerobic conditions","volume":"71","author":"Mourao","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5817","DOI":"10.1007\/s00253-015-6749-0","article-title":"Survival in amoeba\u2014A major selection pressure on the presence of bacterial copper and zinc resistance determinants? Identification of a \u201ccopper pathogenicity island\u201d","volume":"99","author":"Hao","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1111\/1462-2920.15016","article-title":"Tolerance to arsenic contaminant among multidrug-resistant and copper-tolerant Salmonella successful clones is associated with diverse ars operons and genetic contexts","volume":"22","author":"Mourao","year":"2020","journal-title":"Environ. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1046\/j.1365-2672.1999.00853.x","article-title":"The effect of zinc oxide supplementation on the stability of the intestinal flora with special reference to composition of coliforms in weaned pigs","volume":"87","author":"Katouli","year":"1999","journal-title":"J. Appl. Microbiol."},{"key":"ref_64","first-page":"S26","article-title":"Zinc oxide in treating E. coli diarrhea in pigs after weaning","volume":"18","author":"Holm","year":"1996","journal-title":"Comp. Cont. Educ. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/1758-2229.12285","article-title":"Early-life establishment of the swine gut microbiome and impact on host phenotypes","volume":"7","author":"Mach","year":"2015","journal-title":"Environ. Microbiol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hiippala, K., Jouhten, H., Ronkainen, A., Hartikainen, A., Kainulainen, V., Jalanka, J., and Satokari, R. (2018). The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation. Nutrients, 10.","DOI":"10.3390\/nu10080988"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2217\/fmb-2016-0130","article-title":"Roseburia spp.: A marker of health?","volume":"12","author":"Smida","year":"2017","journal-title":"Future Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.anaerobe.2014.06.002","article-title":"Characterization of the fecal microbiome in different swine groups by high-throughput sequencing","volume":"28","author":"Park","year":"2014","journal-title":"Anaerobe"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5266","DOI":"10.1128\/jb.172.9.5266-5277.1990","article-title":"Isolation of the replication and partitioning regions of the Salmonella typhimurium virulence plasmid and stabilization of heterologous replicons","volume":"172","author":"Tinge","year":"1990","journal-title":"J. Bacteriol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1128\/AAC.02412-14","article-title":"In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing","volume":"58","author":"Carattoli","year":"2014","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/11\/1291\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:26:44Z","timestamp":1760178404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/11\/1291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,30]]},"references-count":70,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["genes11111291"],"URL":"https:\/\/doi.org\/10.3390\/genes11111291","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,30]]}}}