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Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans
Mucosa-associated Escherichia coli are frequently found in the colonic mucosa of patients with colorectal adenocarcinoma, but rarely in healthy controls. Chronic mucosal E. coli infection has therefore been linked to colonic tumourigenesis. E. coli strains carrying eae (encoding the bacterial adhesi...
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| Published in: | PloS one 2009-05, Vol.4 (5), p.e5517-e5517 |
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| description | Mucosa-associated Escherichia coli are frequently found in the colonic mucosa of patients with colorectal adenocarcinoma, but rarely in healthy controls. Chronic mucosal E. coli infection has therefore been linked to colonic tumourigenesis. E. coli strains carrying eae (encoding the bacterial adhesion protein intimin) attach intimately to the intestinal mucosa and are classed as attaching and effacing E. coli (AEEC). Enteropathogenic Escherichia coli (EPEC) are the most common form of AEEC identified in man. EPEC utilise a type III secretion system to translocate effector proteins into host cells and infection induces wide-ranging effects on the host cell proteome. We hypothesised that EPEC infection could influence molecular pathways involved in colorectal tumourigenesis.
When co-cultured with human colorectal cell lines, EPEC dramatically downregulated the expression of key DNA mismatch repair proteins MSH2 and MLH1 in an attachment specific manner. Cytochrome c staining and TUNEL analysis confirmed that this effect was not a consequence of apoptosis/necrosis. Ex vivo human colonic mucosa was co-cultured with EPEC and probed by immunofluorescence to locate adherent bacteria. EPEC entered 10% of colonic crypts and adhered to crypt epithelial cells, often in the proliferative compartment. Adenocarcinoma and normal colonic mucosa from colorectal cancer patients (n = 20) was probed by immunofluorescence and PCR for AEEC. Mucosa-associated E. coli were found on 10/20 (50%) adenocarcinomas and 3/20 (15%) normal mucosa samples (P |
| doi_str_mv | 10.1371/journal.pone.0005517 |
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When co-cultured with human colorectal cell lines, EPEC dramatically downregulated the expression of key DNA mismatch repair proteins MSH2 and MLH1 in an attachment specific manner. Cytochrome c staining and TUNEL analysis confirmed that this effect was not a consequence of apoptosis/necrosis. Ex vivo human colonic mucosa was co-cultured with EPEC and probed by immunofluorescence to locate adherent bacteria. EPEC entered 10% of colonic crypts and adhered to crypt epithelial cells, often in the proliferative compartment. Adenocarcinoma and normal colonic mucosa from colorectal cancer patients (n = 20) was probed by immunofluorescence and PCR for AEEC. Mucosa-associated E. coli were found on 10/20 (50%) adenocarcinomas and 3/20 (15%) normal mucosa samples (P<0.05). AEEC were detected on 5/20 (25%) adenocarcinomas, but not normal mucosa samples (P<0.05).
The ability of EPEC to downregulate DNA mismatch repair proteins represents a novel gene-environment interaction that could increase the susceptibility of colonic epithelial cells to mutations and therefore promote colonic tumourigenesis. The potential role of AEEC in colorectal tumourigenesis warrants further investigation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0005517</identifier><identifier>PMID: 19436735</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Adenocarcinoma - microbiology ; Analysis ; Apoptosis ; Bacteria ; Bacterial Adhesion - genetics ; Bacterial infections ; Biopsy ; Cancer ; Cell Line, Tumor ; Chronic infection ; Citrobacter ; Coliforms ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - microbiology ; Crypts ; Cytochrome ; Cytochrome c ; Deoxyribonucleic acid ; Diarrhea ; DNA ; DNA methylation ; DNA repair ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Down-Regulation ; E coli ; Effector cells ; Enteropathogenic Escherichia coli - pathogenicity ; Epithelial cells ; Escherichia coli ; Escherichia coli - pathogenicity ; Escherichia coli - physiology ; Fluorescent Antibody Technique ; Gastroenterology and Hepatology/Gastrointestinal Cancers ; Gastroenterology and Hepatology/Gastrointestinal Infections ; Gene expression ; Genes ; Genetic aspects ; Genetics ; Health aspects ; Helicobacter pylori ; Humans ; Immunofluorescence ; Industrialized nations ; Infection ; Infections ; Infectious diseases ; Intestinal Mucosa - microbiology ; Intestine ; Intimin ; Kinases ; Medicine ; Mismatch repair ; MLH1 protein ; Molecular Biology/DNA Repair ; MSH2 protein ; Mucosa ; Mutation ; Pathology ; Patients ; Phosphorylation ; Proteins ; Proteomes ; Repair ; Studies ; Tumors</subject><ispartof>PloS one, 2009-05, Vol.4 (5), p.e5517-e5517</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Maddocks et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Maddocks et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c721t-a7292af348ab985bd6e98b05ead87d06d4da172d15dea3fa2b8febfba3e48e953</citedby><cites>FETCH-LOGICAL-c721t-a7292af348ab985bd6e98b05ead87d06d4da172d15dea3fa2b8febfba3e48e953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1289216044/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1289216044?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,37012,44589,53790,53792,74997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19436735$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Häcker, Georg</contributor><creatorcontrib>Maddocks, Oliver D K</creatorcontrib><creatorcontrib>Short, Abigail J</creatorcontrib><creatorcontrib>Donnenberg, Michael S</creatorcontrib><creatorcontrib>Bader, Scott</creatorcontrib><creatorcontrib>Harrison, David J</creatorcontrib><title>Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Mucosa-associated Escherichia coli are frequently found in the colonic mucosa of patients with colorectal adenocarcinoma, but rarely in healthy controls. Chronic mucosal E. coli infection has therefore been linked to colonic tumourigenesis. E. coli strains carrying eae (encoding the bacterial adhesion protein intimin) attach intimately to the intestinal mucosa and are classed as attaching and effacing E. coli (AEEC). Enteropathogenic Escherichia coli (EPEC) are the most common form of AEEC identified in man. EPEC utilise a type III secretion system to translocate effector proteins into host cells and infection induces wide-ranging effects on the host cell proteome. We hypothesised that EPEC infection could influence molecular pathways involved in colorectal tumourigenesis.
When co-cultured with human colorectal cell lines, EPEC dramatically downregulated the expression of key DNA mismatch repair proteins MSH2 and MLH1 in an attachment specific manner. Cytochrome c staining and TUNEL analysis confirmed that this effect was not a consequence of apoptosis/necrosis. Ex vivo human colonic mucosa was co-cultured with EPEC and probed by immunofluorescence to locate adherent bacteria. EPEC entered 10% of colonic crypts and adhered to crypt epithelial cells, often in the proliferative compartment. Adenocarcinoma and normal colonic mucosa from colorectal cancer patients (n = 20) was probed by immunofluorescence and PCR for AEEC. Mucosa-associated E. coli were found on 10/20 (50%) adenocarcinomas and 3/20 (15%) normal mucosa samples (P<0.05). AEEC were detected on 5/20 (25%) adenocarcinomas, but not normal mucosa samples (P<0.05).
The ability of EPEC to downregulate DNA mismatch repair proteins represents a novel gene-environment interaction that could increase the susceptibility of colonic epithelial cells to mutations and therefore promote colonic tumourigenesis. The potential role of AEEC in colorectal tumourigenesis warrants further investigation.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - microbiology</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Bacteria</subject><subject>Bacterial Adhesion - genetics</subject><subject>Bacterial infections</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Chronic infection</subject><subject>Citrobacter</subject><subject>Coliforms</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - microbiology</subject><subject>Crypts</subject><subject>Cytochrome</subject><subject>Cytochrome c</subject><subject>Deoxyribonucleic acid</subject><subject>Diarrhea</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA repair</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation</subject><subject>E coli</subject><subject>Effector cells</subject><subject>Enteropathogenic Escherichia coli - pathogenicity</subject><subject>Epithelial cells</subject><subject>Escherichia coli</subject><subject>Escherichia coli - pathogenicity</subject><subject>Escherichia coli - physiology</subject><subject>Fluorescent Antibody Technique</subject><subject>Gastroenterology and Hepatology/Gastrointestinal Cancers</subject><subject>Gastroenterology and Hepatology/Gastrointestinal Infections</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetics</subject><subject>Health aspects</subject><subject>Helicobacter pylori</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Industrialized nations</subject><subject>Infection</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Intestinal Mucosa - microbiology</subject><subject>Intestine</subject><subject>Intimin</subject><subject>Kinases</subject><subject>Medicine</subject><subject>Mismatch repair</subject><subject>MLH1 protein</subject><subject>Molecular Biology/DNA Repair</subject><subject>MSH2 protein</subject><subject>Mucosa</subject><subject>Mutation</subject><subject>Pathology</subject><subject>Patients</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Proteomes</subject><subject>Repair</subject><subject>Studies</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk21r1TAYhosobk7_gWhBGPjhHJukr1-Ew5x6YDjw7Wt4mjw5zWiTsyTd9I_4e023qufIQEkhbXLdd9LnJUmekmxJWEVeXdjRGeiXW2twmWVZUZDqXnJIGkYXJc3Y_Z33g-SR9xeRYXVZPkwOSJOzsmLFYfJjFQKITptNCkamqBSI6ePUiw6djjuQCtvrVNpr43Az9hAwffNhlQ7aDxBElzrcgnbp1tmA2qTxudLB2Rs_cJiC91boKJPptQ7dZGcdigB9ChKNFeDikXYAP2m7cQDjHycPFPQen8zzUfLl7ennk_eLs_N365PV2UJUlIQFVLShoFheQ9vURStLbOo2KxBkXcmslLkEUlFJConAFNC2VtiqFhjmNTYFO0qe3_pue-v5HFLPCa0bSsoszyOxviWkhQu-dXoA951b0PxmwboNBxe06JFLpVTRosiLvM1ZvBGorMUaZIESgDbR6_V82tgOKAWa4KDfM93fMbrjG3vFaVlVeTEZHM8Gzl6O6AOPWRDY92DQjp6XFS1IRsg_QZqVedPEEjhKXvwF3h2EmdpA_E9tlI3XE5MlX-UVixCpJ2p5BxWHxEGLWKZKx_U9wcs9QWQCfgsbGL3n608f_589_7rPHu-wHUIfOm_7MWhr_D6Y34LCWe8dqt-5IBmfuuxXNPjUZXzusih7tpvHP6K5rdhPvrwm8w</recordid><startdate>20090513</startdate><enddate>20090513</enddate><creator>Maddocks, Oliver D K</creator><creator>Short, Abigail J</creator><creator>Donnenberg, Michael S</creator><creator>Bader, Scott</creator><creator>Harrison, David J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7T7</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090513</creationdate><title>Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans</title><author>Maddocks, Oliver D K ; Short, Abigail J ; Donnenberg, Michael S ; Bader, Scott ; Harrison, David J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c721t-a7292af348ab985bd6e98b05ead87d06d4da172d15dea3fa2b8febfba3e48e953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maddocks, Oliver D K</au><au>Short, Abigail J</au><au>Donnenberg, Michael S</au><au>Bader, Scott</au><au>Harrison, David J</au><au>Häcker, Georg</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2009-05-13</date><risdate>2009</risdate><volume>4</volume><issue>5</issue><spage>e5517</spage><epage>e5517</epage><pages>e5517-e5517</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Mucosa-associated Escherichia coli are frequently found in the colonic mucosa of patients with colorectal adenocarcinoma, but rarely in healthy controls. Chronic mucosal E. coli infection has therefore been linked to colonic tumourigenesis. E. coli strains carrying eae (encoding the bacterial adhesion protein intimin) attach intimately to the intestinal mucosa and are classed as attaching and effacing E. coli (AEEC). Enteropathogenic Escherichia coli (EPEC) are the most common form of AEEC identified in man. EPEC utilise a type III secretion system to translocate effector proteins into host cells and infection induces wide-ranging effects on the host cell proteome. We hypothesised that EPEC infection could influence molecular pathways involved in colorectal tumourigenesis.
When co-cultured with human colorectal cell lines, EPEC dramatically downregulated the expression of key DNA mismatch repair proteins MSH2 and MLH1 in an attachment specific manner. Cytochrome c staining and TUNEL analysis confirmed that this effect was not a consequence of apoptosis/necrosis. Ex vivo human colonic mucosa was co-cultured with EPEC and probed by immunofluorescence to locate adherent bacteria. EPEC entered 10% of colonic crypts and adhered to crypt epithelial cells, often in the proliferative compartment. Adenocarcinoma and normal colonic mucosa from colorectal cancer patients (n = 20) was probed by immunofluorescence and PCR for AEEC. Mucosa-associated E. coli were found on 10/20 (50%) adenocarcinomas and 3/20 (15%) normal mucosa samples (P<0.05). AEEC were detected on 5/20 (25%) adenocarcinomas, but not normal mucosa samples (P<0.05).
The ability of EPEC to downregulate DNA mismatch repair proteins represents a novel gene-environment interaction that could increase the susceptibility of colonic epithelial cells to mutations and therefore promote colonic tumourigenesis. The potential role of AEEC in colorectal tumourigenesis warrants further investigation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19436735</pmid><doi>10.1371/journal.pone.0005517</doi><tpages>e5517</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-05, Vol.4 (5), p.e5517-e5517 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1289216044 |
| source | Open Access: PubMed Central; Publicly Available Content Database (Proquest) (PQ_SDU_P3) |
| subjects | Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - metabolism Adenocarcinoma - microbiology Analysis Apoptosis Bacteria Bacterial Adhesion - genetics Bacterial infections Biopsy Cancer Cell Line, Tumor Chronic infection Citrobacter Coliforms Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Colorectal Neoplasms - microbiology Crypts Cytochrome Cytochrome c Deoxyribonucleic acid Diarrhea DNA DNA methylation DNA repair DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Down-Regulation E coli Effector cells Enteropathogenic Escherichia coli - pathogenicity Epithelial cells Escherichia coli Escherichia coli - pathogenicity Escherichia coli - physiology Fluorescent Antibody Technique Gastroenterology and Hepatology/Gastrointestinal Cancers Gastroenterology and Hepatology/Gastrointestinal Infections Gene expression Genes Genetic aspects Genetics Health aspects Helicobacter pylori Humans Immunofluorescence Industrialized nations Infection Infections Infectious diseases Intestinal Mucosa - microbiology Intestine Intimin Kinases Medicine Mismatch repair MLH1 protein Molecular Biology/DNA Repair MSH2 protein Mucosa Mutation Pathology Patients Phosphorylation Proteins Proteomes Repair Studies Tumors |
| title | Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans |
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