{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:47:38Z","timestamp":1785894458486,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Food and Agriculture of the United States Department of Agriculture","award":["NC.X-329-5-20-120-1"],"award-info":[{"award-number":["NC.X-329-5-20-120-1"]}]},{"name":"Agricultural Research Program, North Carolina Agricultural and Technical State University","award":["NC.X-329-5-20-120-1"],"award-info":[{"award-number":["NC.X-329-5-20-120-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Bacitracin Methylene Disalicylate (BMD), as a feed additive to poultry diets, enhances digestion, prevents Salmonella enteritidis (SE) colonization, and treats current infections. The objective of this study was to utilize a quantitative proteomic approach to determine the effect of BMD feed additive on broiler chickens challenged with SE in the spleen proteome. At 1 d of age, chicks were randomly allocated into four groups: control with and without SE challenge (CON, n = 60; CON-SE, n = 60), BMD with and without SE challenge (BMD, n = 60; BMD-SE, n = 60). Birds in the CON-SE and BMD-SE treatment were administered SE inoculum by oral gavage. On day three and day seven post-gavage, the spleen was collected aseptically from birds in each treatment group (CON, n = 4\/day; CON-SE, n = 4\/day; BMD, n = 4\/day; BMD-SE, n = 4\/day). Proteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS\/MS) showed an increased abundance of 115 proteins and decreased of 77 due to the BMD. Proteins that decreased in abundance were enriched for fibrinogen complex and extracellular space, whereas proteins that increased in abundance were enriched for proteasome-mediated ubiquitin-dependent protein catabolic process and mitochondrion. Analysis of the interaction between BMD and the Salmonella challenge found 230 differentially abundant proteins including proteins associated with RNA binding, spliceosome, protein transport, and cell adhesion among the upregulated proteins, and those associated with protein folding, carbon metabolism, biosynthesis of nucleotide sugars, response to oxidative stress, positive regulation of NIK\/NF-kappaB signaling, and inflammatory response among the downregulated proteins. The impact of BMD treatment on spleen proteome indicates an anti-apoptotic effect. BMD also modified the response of the spleen to the SE challenge with a marked decrease in proteins that prompt cytokine synthesis and an increase in proteins involved in the selective removal of unfolded proteins.<\/jats:p>","DOI":"10.3390\/antibiotics13050414","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T03:30:49Z","timestamp":1714534249000},"page":"414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bacitracin Methylene Disalicylate (BMD) Treatment Affects Spleen Proteome in Broiler Chicks Infected with Salmonella enteritidis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6611-126X","authenticated-orcid":false,"given":"Adedeji","family":"Adetunji","sequence":"first","affiliation":[{"name":"Department of Animal Sciences, North Carolina Agricultural and Technical State University, Greensboro, NC 27411, USA"},{"name":"Department of Agriculture, University of Arkansas at Pine Bluff, Pine Bluff, AR 71601, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8835-3550","authenticated-orcid":false,"given":"Theresa","family":"Casey","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4543-1536","authenticated-orcid":false,"given":"Uma K.","family":"Aryal","sequence":"additional","affiliation":[{"name":"Purdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA"},{"name":"Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3098-8492","authenticated-orcid":false,"given":"Tunde","family":"Ogundare","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, North Carolina Agricultural and Technical State University, Greensboro, NC 27411, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackeline","family":"Franco","sequence":"additional","affiliation":[{"name":"Purdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3619-5853","authenticated-orcid":false,"given":"Yewande","family":"Fasina","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, North Carolina Agricultural and Technical State University, Greensboro, NC 27411, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101134","DOI":"10.1016\/j.psj.2021.101134","article-title":"Comparative efficacy of spray-dried plasma and bacitracin methylene disalicylate in reducing cecal colonization by Salmonella enteritidis in broiler chickens","volume":"100","author":"Fasina","year":"2021","journal-title":"Poult. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.18683\/germs.2021.1244","article-title":"Salmonella spp. Infection\u2014A continuous threat worldwide","volume":"11","author":"Popa","year":"2021","journal-title":"Germs"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ehuwa, O., Jaiswal, A.K., and Jaiswal, S. (2021). Salmonella, food safety and food handling practices. Foods, 10.","DOI":"10.3390\/foods10050907"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hiatt, J.R., and Phillips, E.H. (1997). Surgical Diseases of the Spleen, Springer.","DOI":"10.1007\/978-3-642-60574-1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.immuni.2013.10.010","article-title":"The spleen in local and systemic regulation of immunity","volume":"39","author":"Bronte","year":"2013","journal-title":"Immunity"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Adetunji, A., Casey, T., Franco, J., Shah, D., and Fasina, Y. (2022). Proteomic analysis of the effect of Salmonella challenge on broiler chicken. Molecules, 27.","DOI":"10.3390\/molecules27217277"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3592","DOI":"10.1038\/s41598-018-22004-6","article-title":"Antibiotic growth promoters virginiamycin and bacitracin methylene disalicylate alter the chicken intestinal metabolome","volume":"8","author":"Gadde","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1128\/CMR.16.2.175-188.2003","article-title":"Antimicrobial growth promoters used in animal feed: Effects of less well known antibiotics on gram-positive bacteria","volume":"16","author":"Butaye","year":"2003","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8212","DOI":"10.1038\/s41598-019-44338-5","article-title":"In-feed bacitracin methylene disalicylate modulates the turkey microbiota and metabolome in a dose-dependent manner","volume":"9","author":"Johnson","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"D\u00edaz Carrasco, J.M., Redondo, E.A., Pin Viso, N.D., Redondo, L.M., Farber, M.D., and Fern\u00e1ndez Miyakawa, M.E. (2018). Tannins and bacitracin differentially modulate gut microbiota of broiler chickens. BioMed Res. Int., 2018.","DOI":"10.1155\/2018\/1879168"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.2105\/AJPH.2015.302870","article-title":"Antibiotics overuse in animal agriculture: A call to action for health care providers","volume":"105","author":"Martin","year":"2015","journal-title":"Am. J. Public Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1128\/CMR.00002-11","article-title":"Food animals and antimicrobials: Impacts on human health","volume":"24","author":"Marshall","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1744-8603-9-48","article-title":"Restrictions on antimicrobial use in food animal production: An international regulatory and economic survey","volume":"9","author":"Maron","year":"2013","journal-title":"Glob. Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.fct.2019.01.033","article-title":"Importance of antibiotic residues in animal food","volume":"125","year":"2019","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Paul, S.S., Rama Rao, S.V., Hegde, N., Williams, N.J., Chatterjee, R.N., Raju, M.V.L.N., Reddy, G.N., Kumar, V., Phani Kumar, P.S., and Mallick, S. (2022). Effects of dietary antimicrobial growth promoters on performance parameters and abundance and diversity of broiler chicken gut microbiome and selection of antibiotic resistance genes. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.905050"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1161\/CIRCRESAHA.121.320464","article-title":"Yes-associated protein targets the transforming growth factor \u03b2 pathway to mediate high-fat\/high-sucrose diet-induced arterial stiffness","volume":"130","author":"Liu","year":"2022","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1080\/00071668.2013.775404","article-title":"Comparison of gene expression profiles of the jejunum of broilers supplemented with a yeast cell wall-derived mannan oligosaccharide versus bacitractin methylene disalicylate","volume":"54","author":"Brennan","year":"2013","journal-title":"Br. Poult. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, J., Xiao, Y., Fan, Q., Yang, H., Yang, C., Zhang, G., and Chen, S. (2022). Dietary bacitracin methylene disalicylate improves growth performance by mediating the gut microbiota in broilers. Antibiotics, 11.","DOI":"10.3390\/antibiotics11060818"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/j.1749-6632.2001.tb03525.x","article-title":"Tumors and fibrinogen. the role of fibrinogen as an extracellular matrix protein","volume":"936","author":"Rybarczyk","year":"2001","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1046\/j.1365-2141.1996.d01-1731.x","article-title":"Down-regulation of fibrinogen biosynthesis by IL-4, IL-10 and IL-13","volume":"93","author":"Vasse","year":"1996","journal-title":"Br. J. Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hamar, P. (2022). A new role of acute phase proteins: Local production is an ancient, general stress-response system of mammalian cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23062972"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"735","DOI":"10.18388\/abp.2003_3664","article-title":"Inter-alpha-inhibitor, hyaluronan and inflammation","volume":"50","author":"Fries","year":"2003","journal-title":"Acta Biochim. Pol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0092-8674(00)80954-X","article-title":"The actin cytoskeleton and lymphocyte activation","volume":"96","author":"Penninger","year":"1999","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Satou, R., Franco, M., Dugas, C.M., Katsurada, A., and Navar, L.G. (2022). Immunosuppression by mycophenolate mofetil mitigates intrarenal angiotensinogen augmentation in angiotensin II-dependent hypertension. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147680"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0092-8674(03)01074-2","article-title":"Back to the future with ubiquitin","volume":"116","author":"Pickart","year":"2004","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1681\/ASN.2006010083","article-title":"Protein degradation by the ubiquitin-proteasome pathway in normal and disease states","volume":"17","author":"Lecker","year":"2006","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev.bb.22.060193.001011","article-title":"Prolyl isomerase: Enzymatic catalysis of slow protein-folding reactions","volume":"22","author":"Schmid","year":"1993","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.cell.2014.10.042","article-title":"The structural basis of substrate recognition by the eukaryotic chaperonin TRiC\/CCT","volume":"159","author":"Joachimiak","year":"2014","journal-title":"Cell"},{"key":"ref_30","first-page":"275","article-title":"Protein folding and diseases","volume":"38","author":"Lee","year":"2005","journal-title":"J. Biochem. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/s41419-020-03040-5","article-title":"EFTUD2 maintains the survival of tumor cells and promotes hepatocellular carcinoma progression via the activation of STAT3","volume":"11","author":"Tu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109210","DOI":"10.1016\/j.celrep.2021.109210","article-title":"Lactate dehydrogenase A-dependent aerobic glycolysis promotes natural killer cell anti-viral and anti-tumor function","volume":"35","author":"Sheppard","year":"2021","journal-title":"Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Soubise, B., Jiang, Y., Douet-Guilbert, N., and Troadec, M. (2022). RBM22, a key player of pre-mRNA splicing and gene expression regulation, is altered in cancer. Cancers, 14.","DOI":"10.3390\/cancers14030643"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"889","DOI":"10.17219\/acem\/147271","article-title":"RPS27 selectively regulates the expression and alternative splicing of inflammatory and immune response genes in thyroid cancer cells","volume":"31","author":"Wan","year":"2022","journal-title":"Adv. Clin. Exp. Med. Off. Organ Wroc. Med. Univ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e02525-20","DOI":"10.1128\/mBio.02525-20","article-title":"CRNKL1 is a highly selective regulator of intron-retaining HIV-1 and cellular mRNAs","volume":"12","author":"Xiao","year":"2021","journal-title":"mBio"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1469-7580.1998.19310001.x","article-title":"The role of laminins in basement membrane function","volume":"193","author":"Aumailley","year":"1998","journal-title":"J. Anat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s42826-019-0018-9","article-title":"Lipopolysaccharide induces neuroglia activation and NF-\u03baB activation in cerebral cortex of adult mice","volume":"35","author":"Kang","year":"2019","journal-title":"Lab. Anim. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"103193","DOI":"10.1016\/j.jri.2020.103193","article-title":"Impact of lipopolysaccharide administration on luteinizing hormone\/choriogonadotropin receptor (lhcgr) expression in mouse ovaries","volume":"142","author":"Adetunji","year":"2020","journal-title":"J. Reprod. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8923","DOI":"10.3892\/mmr.2017.7693","article-title":"Rapamycin promotes osteogenesis under inflammatory conditions","volume":"16","author":"Li","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.it.2012.04.006","article-title":"Tertiary lymphoid organs in infection and autoimmunity","volume":"33","author":"Neyt","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bbrc.2022.08.070","article-title":"Global landscape of protein complexes in postprandial-state livers from diet-induced obese and lean mice","volume":"629","author":"Kim","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kim, S.Q., Mohallem, R., Franco, J., Buhman, K.K., Kim, K., and Aryal, U.K. (2022). Multi-omics approach reveals dysregulation of protein phosphorylation correlated with lipid metabolism in mouse non-alcoholic fatty liver. Cells, 11.","DOI":"10.1101\/2022.02.16.480672"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in ingenuity pathway analysis","volume":"30","author":"Green","year":"2014","journal-title":"Bioinformatics"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/5\/414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:37:57Z","timestamp":1760107077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/5\/414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,1]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["antibiotics13050414"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics13050414","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,1]]}}}