{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:27:30Z","timestamp":1791426450447,"version":"4.3.3"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2020.564953","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T05:38:46Z","timestamp":1605591526000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Pic Protein From Enteroaggregative E. coli Induces Different Mechanisms for Its Dual Activity as a Mucus Secretagogue and a Mucinase"],"prefix":"10.3389","volume":"11","author":[{"given":"Fernando","family":"Flores-Sanchez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Chavez-Due\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Sanchez-Villamil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Navarro-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000117","article-title":"Mucus layers in inflammatory bowel disease","volume":"20","author":"Johansson","year":"2014","journal-title":"Inflamm Bowel Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/glycob\/8.1.67","article-title":"The oligomerization of a family of four genetically clustered human gastrointestinal mucins","volume":"8","author":"van Klinken","year":"1998","journal-title":"Glycobiology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izaa064","article-title":"Muc5ac Expression Protects the Colonic Barrier in Experimental Colitis","volume":"26","author":"Olli","year":"2020","journal-title":"Inflamm Bowel Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006451107","article-title":"The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions","author":"Johansson","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.45.31751","article-title":"The structure and assembly of secreted mucins","volume":"274","author":"Perez-Vilar","year":"1999","journal-title":"J Biol Chem"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1042\/bj3350381","article-title":"Human MUC5AC mucin dimerizes in the rough endoplasmic reticulum, similarly to the MUC2 mucin","volume":"335","author":"Asker","year":"1998","journal-title":"Biochem J"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208483200","article-title":"The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment","volume":"277","author":"Godl","year":"2002","journal-title":"J Biol Chem"},{"key":"B8","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nrc1251","article-title":"Mucins in cancer: protection and control of the cell surface","volume":"4","author":"Hollingsworth","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.26086-0","article-title":"Haemagglutinin\/protease expression and mucin gel penetration in El Tor biotype Vibrio cholerae","volume":"149","author":"Silva","year":"2003","journal-title":"Microbiol (Reading)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/iai.71.2.838-844.2003","article-title":"Entamoeba histolytica cysteine proteinases disrupt the polymeric structure of colonic mucin and alter its protective function","volume":"71","author":"Moncada","year":"2003","journal-title":"Infect Immun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12717","article-title":"The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo","volume":"19","author":"Hews","year":"2017","journal-title":"Cell Microbiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117486","article-title":"Pathogenic E. coli exploits SslE mucinase activity to translocate through the mucosal barrier and get access to host cells","volume":"10","author":"Valeri","year":"2015","journal-title":"PloS One"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2012.01008.x","article-title":"Enteroaggregative Escherichia coli pathotype: a genetically heterogeneous emerging foodborne enteropathogen","volume":"66","author":"Estrada-Garcia","year":"2012","journal-title":"FEMS Immunol Med Microbiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.64.11.4761-4768.1996","article-title":"T84 cells in culture as a model for enteroaggregative Escherichia coli pathogenesis","volume":"64","author":"Nataro","year":"1996","journal-title":"Infect Immun"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/158.1.70","article-title":"Characterization of enteroadherent-aggregative Escherichia coli, a putative agent of diarrheal disease","volume":"158","author":"Vial","year":"1988","journal-title":"J Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1128\/IAI.58.3.794-800.1990","article-title":"Characterization of binding of Escherichia coli strains which are enteropathogens to small-bowel mucin","volume":"58","author":"Wanke","year":"1990","journal-title":"Infect Immun"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/171.2.465","article-title":"Heterogeneity of enteroaggregative Escherichia coli virulence demonstrated in volunteers","volume":"171","author":"Nataro","year":"1995","journal-title":"J Infect Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro818","article-title":"Pathogenic Escherichia coli","volume":"2","author":"Kaper","year":"2004","journal-title":"Nat Rev Microbiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2004.08.008","article-title":"Antibody response against plasmid-encoded toxin (Pet) and the protein involved in intestinal colonization (Pic) in children with diarrhea produced by enteroaggregative Escherichia coli","volume":"43","author":"Bellini","year":"2005","journal-title":"FEMS Immunol Med Microbiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1128\/MMBR.68.4.692-744.2004","article-title":"Type V protein secretion pathway: the autotransporter story","volume":"68","author":"Henderson","year":"2004","journal-title":"Microbiol Mol Biol Rev MMBR"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00523-10","article-title":"Pic, an autotransporter protein secreted by different pathogens in the Enterobacteriaceae family, is a potent mucus secretagogue","volume":"78","author":"Navarro-Garcia","year":"2010","journal-title":"Infect Immun"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/toxins2051134","article-title":"Host-Toxin Interactions Involving EspC and Pet, Two Serine Protease Autotransporters of the Enterobacteriaceae","volume":"2","author":"Navarro-Garcia","year":"2010","journal-title":"Toxins"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2008.04.006","article-title":"The serine protease motif of Pic mediates a dose-dependent mucolytic activity after binding to sugar constituents of the mucin substrate","volume":"45","author":"Gutierrez-Jimenez","year":"2008","journal-title":"Microb Pathog"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.11.5587-5596.1999","article-title":"Characterization of pic, a secreted protease of Shigella flexneri and enteroaggregative Escherichia coli","volume":"67","author":"Henderson","year":"1999","journal-title":"Infect Immun"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101006108","article-title":"Serine protease autotransporters from Shigella flexneri and pathogenic Escherichia coli target a broad range of leukocyte glycoproteins","volume":"108","author":"Ruiz-Perez","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01494-08","article-title":"The Pic protease of enteroaggregative Escherichia coli promotes intestinal colonization and growth in the presence of mucin","volume":"77","author":"Harrington","year":"2009","journal-title":"Infect Immun"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01078-13","article-title":"EatA, an immunogenic protective antigen of enterotoxigenic Escherichia coli, degrades intestinal mucin","volume":"82","author":"Kumar","year":"2014","journal-title":"Infect Immun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-005-0973-z","article-title":"Tanshinone IIA isolated from Salvia miltiorrhiza elicits the cell death of human endothelial cells","volume":"12","author":"Yang","year":"2005","journal-title":"J Biomed Sci"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s10156-013-0554-4","article-title":"Interplay of flagellar motility and mucin degradation stimulates the association of Pseudomonas aeruginosa with human epithelial colorectal adenocarcinoma (Caco-2) cells","volume":"19","author":"Hayashi","year":"2013","journal-title":"J infection Chemother"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2011.12.016","article-title":"Flagellin\/TLR5 responses induce mucus hypersecretion by activating EGFR via an epithelial cell signaling cascades","volume":"318","author":"Yu","year":"2012","journal-title":"Exp Cell Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2003.t01-1-01163.x","article-title":"mRNA of MUC2 is stimulated by IL-4, IL-13 or TNF-alpha through a mitogen-activated protein kinase pathway in human colon cancer cells","volume":"81","author":"Iwashita","year":"2003","journal-title":"Immunol Cell Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.149310","article-title":"Munc13-2-\/- baseline secretion defect reveals source of oligomeric mucins in mouse airways","volume":"586","author":"Zhu","year":"2008","journal-title":"J Physiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M807849200","article-title":"Synaptotagmin 2 couples mucin granule exocytosis to Ca2+ signaling from endoplasmic reticulum","volume":"284","author":"Tuvim","year":"2009","journal-title":"J Biol Chem"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00359.2002","article-title":"Mucin secretion and PKC isoforms in SPOC1 goblet cells: differential activation by purinergic agonist and PMA","volume":"285","author":"Abdullah","year":"2003","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e1005579s","DOI":"10.1371\/journal.ppat.1005579","article-title":"Entamoeba histolytica Cysteine Proteinase 5 Evokes Mucin Exocytosis from Colonic Goblet Cells via alphavbeta3 Integrin","volume":"12","author":"Cornick","year":"2016","journal-title":"PloS Pathog"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2008.01.007","article-title":"Effect of OPC-12759 on EGF receptor activation, p44\/p42 MAPK activity, and secretion in conjunctival goblet cells","volume":"86","author":"Rios","year":"2008","journal-title":"Exp Eye Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7647","article-title":"Rebamipide upregulates mucin secretion of intestinal goblet cells via Akt phosphorylation","volume":"16","author":"Yasuda-Onozawa","year":"2017","journal-title":"Mol Med Rep"},{"key":"B38","article-title":"Effects of prostaglandin E1, administered by gastric intubation, on mucus secretory patterns in rat small intestine","volume":"8","author":"Cassidy","year":"1980","journal-title":"Adv Prostaglandin Thromboxane Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22455","article-title":"Targeting G-protein coupled receptor-related signaling pathway in a murine xenograft model of appendiceal Pseudomyxoma peritonei","volume":"8","author":"Dilly","year":"2017","journal-title":"Oncotarget"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.55","article-title":"Bacteroidales recruit IL-6-producing intraepithelial lymphocytes in the colon to promote barrier integrity","volume":"11","author":"Kuhn","year":"2018","journal-title":"Mucosal Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2002.17.6.765","article-title":"Interleukin-1beta induces MUC2 gene expression and mucin secretion via activation of PKC-MEK\/ERK, and PI3K in human airway epithelial cells","volume":"17","author":"Kim","year":"2002","journal-title":"J Korean Med Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2016.00120","article-title":"Pathogenic Lifestyles of E. coli Pathotypes in a Standardized Epithelial Cell Model Influence Inflammatory Signaling Pathways and Cytokines Secretion","volume":"6","author":"Sanchez-Villamil","year":"2016","journal-title":"Front Cell infection Microbiol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00025-15","article-title":"The Serine Protease Autotransporter Pic Modulates Citrobacter rodentium Pathogenesis and Its Innate Recognition by the Host","volume":"83","author":"Bhullar","year":"2015","journal-title":"Infect Immun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.30.18857","article-title":"Dimerization of the human MUC2 mucin in the endoplasmic reticulum is followed by a N-glycosylation-dependent transfer of the mono- and dimers to the Golgi apparatus","volume":"273","author":"Asker","year":"1998","journal-title":"J Biol Chem"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.06215.x","article-title":"Mapping of the 45M1 epitope to the C-terminal cysteine-rich part of the human MUC5AC mucin","volume":"275","author":"Lidell","year":"2008","journal-title":"FEBS J"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.459479","article-title":"Site-specific O-glycosylation on the MUC2 mucin protein inhibits cleavage by the Porphyromonas gingivalis secreted cysteine protease (RgpB)","volume":"288","author":"van der Post","year":"2013","journal-title":"J Biol Chem"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803124105","article-title":"The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria","volume":"105","author":"Johansson","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600623103","article-title":"Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel","volume":"103","author":"Lidell","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2746","article-title":"How glycan metabolism shapes the human gut microbiota","volume":"10","author":"Koropatkin","year":"2012","journal-title":"Nat Rev Microbiol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2016.02.010","article-title":"The Densely O-Glycosylated MUC2 Mucin Protects the Intestine and Provides Food for the Commensal Bacteria","volume":"428","author":"Arike","year":"2016","journal-title":"J Mol Biol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1146\/annurev.physiol.70.113006.100638","article-title":"Regulated airway goblet cell mucin secretion","volume":"70","author":"Davis","year":"2008","journal-title":"Annu Rev Physiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.4161\/21688370.2014.982426","article-title":"Roles and regulation of the mucus barrier in the gut","volume":"3","author":"Cornick","year":"2015","journal-title":"Tissue Barriers"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050325","article-title":"Differential stimulation of intestinal mucin secretion by cholera toxin and carbachol","volume":"433","author":"Epple","year":"1997","journal-title":"Pflugers Arch Eur J Physiol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300096200","article-title":"Interleukin-1 beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK\/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells","volume":"278","author":"Song","year":"2003","journal-title":"J Biol Chem"},{"key":"B55","article-title":"The fast release of mucin secretion from human colonic cells induced by Entamoeba histolytica is dependent on contact and protein kinase C activation","volume":"23","author":"Keller","year":"1992","journal-title":"Arch Med Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(00)80477-x","article-title":"IL-13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis","volume":"8","author":"Urban","year":"1998","journal-title":"Immunity"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v113.pm9247474","article-title":"Role of T helper 2 cells in intestinal goblet cell hyperplasia in mice infected with Trichinella spiralis","volume":"113","author":"Ishikawa","year":"1997","journal-title":"Gastroenterology"},{"key":"B58","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/j.1365-3024.2010.01258.x","article-title":"Changes in the mucosal barrier during acute and chronic Trichuris muris infection","volume":"33","author":"Hasnain","year":"2011","journal-title":"Parasite Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2015.12.006","article-title":"Vasopressin-induced Ca(2+) signals in human adipose-derived stem cells","volume":"59","author":"Tran","year":"2016","journal-title":"Cell Calcium"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2005.05035.x","article-title":"Human airway trypsin-like protease induces amphiregulin release through a mechanism involving protease-activated receptor-2-mediated ERK activation and TNF alpha-converting enzyme activity in airway epithelial cells","volume":"272","author":"Chokki","year":"2005","journal-title":"FEBS J"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2013.02.013","article-title":"Human airway trypsin-like protease induces mucin5AC hypersecretion via a protease-activated receptor 2-mediated pathway in human airway epithelial cells","volume":"535","author":"Liu","year":"2013","journal-title":"Arch Biochem Biophys"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/s1471-4892(01)00099-6","article-title":"Protease-activated receptors: how proteases signal to cells","volume":"1","author":"Schmidlin","year":"2001","journal-title":"Curr Opin Pharmacol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.564953\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T05:38:50Z","timestamp":1605591530000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.564953\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,17]]},"references-count":62,"alternative-id":["10.3389\/fimmu.2020.564953"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.564953","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,17]]},"article-number":"564953"}}