{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:26:06Z","timestamp":1784640366537,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Natural Science Foundation of Jiangsu","award":["BK20221516"],"award-info":[{"award-number":["BK20221516"]}]},{"name":"the National Natural Science Foundation of Jiangsu","award":["32172267"],"award-info":[{"award-number":["32172267"]}]},{"name":"the National Natural Science Foundation of Jiangsu","award":["202110307047"],"award-info":[{"award-number":["202110307047"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["BK20221516"],"award-info":[{"award-number":["BK20221516"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172267"],"award-info":[{"award-number":["32172267"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["202110307047"],"award-info":[{"award-number":["202110307047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Program for Student Innovation through Research and Training","award":["BK20221516"],"award-info":[{"award-number":["BK20221516"]}]},{"name":"Program for Student Innovation through Research and Training","award":["32172267"],"award-info":[{"award-number":["32172267"]}]},{"name":"Program for Student Innovation through Research and Training","award":["202110307047"],"award-info":[{"award-number":["202110307047"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>L. monocytogenes, consisting of 13 serotypes, is an opportunistic food-borne pathogen that causes different host reactions depending on its serotypes. In this study, highly toxic L. monocytogenes\u00a010403s resulted in more severe infections and lower survival rates. Additionally, to investigate the remodeling of the host proteome by strains exhibiting differential toxicity, the cellular protein responses of intestinal organoids were analyzed using tandem mass tag (TMT) labeling and high-performance liquid chromatography\u2013mass spectrometry. The virulent strain 10403s caused 102 up-regulated and 52 down-regulated proteins, while the low virulent strain M7 caused 188 up-regulated and 25 down-regulated proteins. Based on the analysis of gene ontology (GO) and KEGG databases, the expressions of differential proteins in organoids infected by L. monocytogenes\u00a010403s (virulent strain) or M7 (low virulent strain) were involved in regulating essential processes such as the biological metabolism, the energy metabolism, and immune system processes. The results showed that the immune system process, as the primary host defense response to L. monocytogenes, comprised five pathways, including ECM\u2013receptor interaction, the complement and coagulation cascades, HIF-1, ferroptosis, and NOD-like receptor signaling pathways. As for the L. monocytogenes\u00a010403s vs. M7 group, the expression of differential proteins was involved in two pathways: systemic lupus erythematosus and transcriptional mis-regulation in cancer. All in all, these results revealed that L. monocytogenes strains with different toxicity induced similar biological functions and immune responses while having different regulations on differential proteins in the pathway.<\/jats:p>","DOI":"10.3390\/ijms23116231","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:05:02Z","timestamp":1654167902000},"page":"6231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["TMT-Based Quantitative Proteomic Analysis of Intestinal Organoids Infected by Listeria monocytogenes Strains with Different Virulence"],"prefix":"10.3390","volume":"23","author":[{"given":"Cong","family":"Zhou","sequence":"first","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafang","family":"Zou","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeyu","family":"Wei","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keping","family":"Ye","sequence":"additional","affiliation":[{"name":"Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"ref_1","first-page":"157","article-title":"Listeria Monocytogenes: A Food-Borne Pathogen","volume":"Volume 15","author":"Thakur","year":"2018","journal-title":"Foodborne Diseases"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ijmm.2010.05.002","article-title":"Listeria monocytogenes lineages: Genomics, evolution, ecology, and phenotypic characteristics","volume":"301","author":"Orsi","year":"2011","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4002","DOI":"10.3389\/fmicb.2021.738470","article-title":"Landscape of Stress Response and Virulence Genes Among Listeria monocytogenes Strains","volume":"12","author":"Lakicevic","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Metz, Z.P., Ding, T., and Baumler, D.J. (2018). Using genome-scale metabolic models to compare serovars of the foodborne pathogen Listeria monocytogenes. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198584"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1128\/CMR.14.3.584-640.2001","article-title":"Listeria Pathogenesis and Molecular Virulence Determinants","volume":"14","author":"Kuhn","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Roche, S.M., Gr\u00e9pinet, O., Kerouanton, A., Ragon, M., Leclercq, A., T\u00e9moin, S., Schaeffer, B., Skorski, G., Mereghetti, L., and Le Monnier, A. (2012). Polyphasic characterization and genetic relatedness of low-virulence and virulent Listeria monocytogenes isolates. BMC Microbiol., 12.","DOI":"10.1186\/1471-2180-12-304"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5563","DOI":"10.1128\/AEM.00319-08","article-title":"Differences in survival among 13 Listeria monocytogenes strains in a dynamic model of the stomach and small intestine","volume":"74","author":"Geornaras","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.4315\/0362-028X.JFP-13-423","article-title":"Low, Medium, and High Heat Tolerant Strains of Listeria monocytogenes and Increased Heat Stress Resistance after Exposure to Sublethal Heat","volume":"77","author":"Shen","year":"2014","journal-title":"J. Food Prot."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1292\/jvms.16-0575","article-title":"Listeria monocytogenes serotype 4b strains replicate in monocytes\/macrophages more than the other serotypes","volume":"79","author":"Hasebe","year":"2017","journal-title":"J. Vet. Med Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fvets.2020.00088","article-title":"Two Prevalent Listeria ivanovii subsp. ivanovii Clonal Strains with Different Virulence Exist in Wild Rodents and Pikas of China","volume":"7","author":"Gan","year":"2020","journal-title":"Front. Vet. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"fnv018","DOI":"10.1093\/femsle\/fnv018","article-title":"Evaluation of transcription levels of inlA, inlB, hly, bsh and prfA genes in Listeria monocytogenes strains using quantitative reverse-transcription PCR and ability of invasion into human CaCo-2 cells","volume":"362","author":"Tamburro","year":"2015","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1177\/039463200301600205","article-title":"Heterogeneity of Virulence-Related Properties inListeria MonocytogenesStrains Isolated from Patients with Haematological Malignancies","volume":"16","author":"Longhi","year":"2003","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19587","DOI":"10.1038\/s41598-019-56028-3","article-title":"Characterization of the pathogenesis and immune response to Listeria monocytogenes strains isolated from a sustained national outbreak","volume":"9","author":"Ghosh","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1038\/s41467-019-10380-0","article-title":"Hypervirulent Listeria monocytogenes clones\u2019 adaption to mammalian gut accounts for their association with dairy products","volume":"10","author":"Maury","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e00397-18","DOI":"10.1128\/IAI.00397-18","article-title":"In Vivo Virulence Characterization of Pregnancy-Associated Listeria monocytogenes Infections","volume":"86","author":"Morrison","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.jprot.2011.05.008","article-title":"Proteomic expression profiles of virulent and avirulent strains of Listeria monocytogenes isolated from macrophages","volume":"74","author":"Donaldson","year":"2011","journal-title":"J. Proteom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1128\/AEM.69.6.3640-3645.2003","article-title":"Adhesion, invasion, and translocation characteristics of Listeria monocytogenes serotypes in Caco-2 cell and mouse models","volume":"69","author":"Jaradat","year":"2003","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.chom.2018.03.004","article-title":"Listeria Adhesion Protein Induces Intestinal Epithelial Barrier Dysfunction for Bacterial Translocation","volume":"23","author":"Drolia","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.micinf.2007.05.008","article-title":"Innate and adaptive immune responses to Listeria monocytogenes: A short overview","volume":"9","author":"Zenewicz","year":"2007","journal-title":"Microbes Infect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1111\/j.1462-5822.2009.01294.x","article-title":"Listeria monocytogenes infection in the face of innate immunity","volume":"11","author":"Corr","year":"2009","journal-title":"Cell. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/intimm\/dxy065","article-title":"Recent progress in organoid culture to model intestinal epithelial barrier functions","volume":"31","author":"Nakamura","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/mi.2014.72","article-title":"A small intestinal organoid model of non-invasive enteric pathogen\u2013epithelial cell interactions","volume":"8","author":"Wilson","year":"2015","journal-title":"Mucosal Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1795389","DOI":"10.1080\/19490976.2020.1795389","article-title":"Research in a time of enteroids and organoids: How the human gut model has transformed the study of enteric bacterial pathogens","volume":"12","author":"Ranganathan","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.foodres.2017.06.051","article-title":"Comparative proteomic analysis of Cronobacter sakazakii by iTRAQ provides insights into response to desiccation","volume":"100","author":"Hu","year":"2017","journal-title":"Food Res. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1586\/14789450.2015.1042867","article-title":"Current strategies and findings in clinically relevant post-translational modification-specific proteomics","volume":"12","author":"Pagel","year":"2015","journal-title":"Expert Rev. Proteom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1128\/AEM.01847-08","article-title":"Comparative Proteomic Analysis of Listeria monocytogenes Strains F2365 and EGD","volume":"75","author":"Donaldson","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e01038-18","DOI":"10.1128\/MRA.01038-18","article-title":"Draft Whole-Genome Sequences of Seven Listeria monocytogenes Strains with Variations in Virulence and Stress Responses","volume":"7","author":"Liu","year":"2018","journal-title":"Microbiol. Resour. Announc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1002\/pmic.200401024","article-title":"Comparative proteome analysis of secretory proteins from pathogenic and nonpathogenic Listeria species","volume":"5","author":"Trost","year":"2005","journal-title":"Proteomics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.mib.2021.11.015","article-title":"Listeriosis, a model infection to study host-pathogen interactions in vivo","volume":"66","author":"Kammoun","year":"2022","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.tim.2018.12.007","article-title":"Crossing the Intestinal Barrier via Listeria Adhesion Protein and Internalin A","volume":"27","author":"Drolia","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fcimb.2014.00009","article-title":"Listeria monocytogenes: Survival and adaptation in the gastrointestinal tract","volume":"4","author":"Gahan","year":"2014","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1099\/mic.0.030205-0","article-title":"The interaction between Listeria monocytogenes and the host gastrointestinal tract","volume":"155","author":"Sleator","year":"2009","journal-title":"Microbiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1074\/mcp.RA118.000767","article-title":"Rapid Remodeling of the Host Epithelial Cell Proteome by the Listeriolysin O (LLO) Pore-forming Toxin","volume":"17","author":"Malet","year":"2018","journal-title":"Mol. Cell. Proteom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s11658-019-0162-0","article-title":"Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer","volume":"24","author":"Bao","year":"2019","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1111\/j.1574-6976.2012.00340.x","article-title":"Human pathogens utilize host extracellular matrix proteins laminin and collagen for adhesion and invasion of the host","volume":"36","author":"Singh","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Speziale, P., Arciola, C.R., and Pietrocola, G. (2019). Fibronectin and Its Role in Human Infective Diseases. Cells, 8.","DOI":"10.3390\/cells8121516"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41422-019-0164-5","article-title":"The molecular machinery of regulated cell death","volume":"29","author":"Tang","year":"2019","journal-title":"Cell Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00281-011-0280-x","article-title":"Interactions between coagulation and complement\u2014Their role in inflammation","volume":"34","author":"Oikonomopoulou","year":"2012","journal-title":"Semin. Immunopathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1038\/ni1412","article-title":"Nod-like proteins in immunity, inflammation and disease","volume":"7","author":"Fritz","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.jcmgh.2018.10.009","article-title":"NOD2 Expression in Intestinal Epithelial Cells Protects Toward the Development of Inflammation and Associated Carcinogenesis","volume":"7","author":"Ferrand","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1126\/science.1104911","article-title":"Nod2-Dependent Regulation of Innate and Adaptive Immunity in the Intestinal Tract","volume":"307","author":"Kobayashi","year":"2005","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2147\/JIR.S137606","article-title":"NOD2 and inflammation: Current insights","volume":"11","author":"Negroni","year":"2018","journal-title":"J. Inflamm. Res."},{"key":"ref_43","unstructured":"Xiao, J., and Feng, X. (2018, January 30). NOD2 is Involved in Regulating MDP-Induced Dentin Differentiation of Dental Pulp Stem Cells. Proceedings of the Ninth General Stomatology Academic Conference of Chinese Stomatological Society, Shanghai, China."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15813","DOI":"10.1073\/pnas.0907722106","article-title":"Nod2 is required for the regulation of commensal microbiota in the intestine","volume":"106","author":"Hrncir","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"19605","DOI":"10.1074\/jbc.M111.221077","article-title":"The NLR adaptor ASC\/PYCARD regulates DUSP10, mitogen-activated protein kinase (MAPK), and chemokine induction independent of the inflammasome","volume":"286","author":"Taxman","year":"2011","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:23:46Z","timestamp":1760138626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/11\/6231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,2]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23116231"],"URL":"https:\/\/doi.org\/10.3390\/ijms23116231","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,2]]}}}