Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions
Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is acco...
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| description | Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens. |
| doi_str_mv | 10.1371/journal.pntd.0005586 |
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Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0005586</identifier><identifier>PMID: 28531220</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adhesins ; Adhesins, Bacterial - metabolism ; Adhesion ; Antibodies ; Bacteria ; Bacterial Adhesion ; Bacterial Toxins - metabolism ; Biology and Life Sciences ; Caco-2 Cells ; Cells ; Colonization ; Colonization factor ; Countries ; Developing countries ; Diabetes ; Diarrhea ; E coli ; Enterocytes ; Enterotoxigenic Escherichia coli - pathogenicity ; Enterotoxins ; Enterotoxins - metabolism ; Epithelial cells ; Epithelial Cells - microbiology ; Epithelium ; Escherichia coli ; Escherichia coli Proteins - metabolism ; Fimbriae, Bacterial - metabolism ; Funding ; Genes ; Genomes ; Grants ; Heat ; Host-Pathogen Interactions ; Humans ; In vitro methods and tests ; Infectious diseases ; Interactions ; Internal medicine ; Intestine ; Kidney diseases ; Laboratories ; LDCs ; Mannans ; Mannose ; Medicine ; Medicine and Health Sciences ; Molecules ; Monolayers ; Monomolecular films ; Mutagenesis ; Mutants ; Pathogenesis ; Pathogens ; Pili ; Plasmids ; Protein Transport ; Proteins ; Specificity ; Stem cells ; Thermal stability ; Toxins ; Transcription ; Tropical diseases ; Veterans ; Virulence ; Virulence (Microbiology)</subject><ispartof>PLoS neglected tropical diseases, 2017-05, Vol.11 (5), p.e0005586</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: pathogen-host interactions. PLoS Negl Trop Dis 11(5): e0005586. https://doi.org/10.1371/journal.pntd.0005586</rights><rights>2017 Sheikh et al 2017 Sheikh et al</rights><rights>2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: pathogen-host interactions. PLoS Negl Trop Dis 11(5): e0005586. https://doi.org/10.1371/journal.pntd.0005586</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-50ef77e79239b135194ab836d981dba40c96ece56c3ea2c9d8d869f33893878e3</citedby><cites>FETCH-LOGICAL-c624t-50ef77e79239b135194ab836d981dba40c96ece56c3ea2c9d8d869f33893878e3</cites><orcidid>0000-0002-2972-6978 ; 0000-0002-1148-697X ; 0000-0003-1085-0589</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456409/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456409/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28531220$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sheikh, Alaullah</creatorcontrib><creatorcontrib>Rashu, Rasheduzzaman</creatorcontrib><creatorcontrib>Begum, Yasmin Ara</creatorcontrib><creatorcontrib>Kuhlman, F Matthew</creatorcontrib><creatorcontrib>Ciorba, Matthew A</creatorcontrib><creatorcontrib>Hultgren, Scott J</creatorcontrib><creatorcontrib>Qadri, Firdausi</creatorcontrib><creatorcontrib>Fleckenstein, James M</creatorcontrib><title>Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens.</description><subject>Adhesins</subject><subject>Adhesins, Bacterial - metabolism</subject><subject>Adhesion</subject><subject>Antibodies</subject><subject>Bacteria</subject><subject>Bacterial Adhesion</subject><subject>Bacterial Toxins - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Caco-2 Cells</subject><subject>Cells</subject><subject>Colonization</subject><subject>Colonization factor</subject><subject>Countries</subject><subject>Developing countries</subject><subject>Diabetes</subject><subject>Diarrhea</subject><subject>E coli</subject><subject>Enterocytes</subject><subject>Enterotoxigenic Escherichia coli - pathogenicity</subject><subject>Enterotoxins</subject><subject>Enterotoxins - metabolism</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - microbiology</subject><subject>Epithelium</subject><subject>Escherichia coli</subject><subject>Escherichia coli Proteins - metabolism</subject><subject>Fimbriae, Bacterial - metabolism</subject><subject>Funding</subject><subject>Genes</subject><subject>Genomes</subject><subject>Grants</subject><subject>Heat</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>In vitro methods and tests</subject><subject>Infectious diseases</subject><subject>Interactions</subject><subject>Internal medicine</subject><subject>Intestine</subject><subject>Kidney diseases</subject><subject>Laboratories</subject><subject>LDCs</subject><subject>Mannans</subject><subject>Mannose</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Molecules</subject><subject>Monolayers</subject><subject>Monomolecular films</subject><subject>Mutagenesis</subject><subject>Mutants</subject><subject>Pathogenesis</subject><subject>Pathogens</subject><subject>Pili</subject><subject>Plasmids</subject><subject>Protein Transport</subject><subject>Proteins</subject><subject>Specificity</subject><subject>Stem cells</subject><subject>Thermal stability</subject><subject>Toxins</subject><subject>Transcription</subject><subject>Tropical diseases</subject><subject>Veterans</subject><subject>Virulence</subject><subject>Virulence 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conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions</title><author>Sheikh, Alaullah ; Rashu, Rasheduzzaman ; Begum, Yasmin Ara ; Kuhlman, F Matthew ; Ciorba, Matthew A ; Hultgren, Scott J ; Qadri, Firdausi ; Fleckenstein, James M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-50ef77e79239b135194ab836d981dba40c96ece56c3ea2c9d8d869f33893878e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adhesins</topic><topic>Adhesins, Bacterial - metabolism</topic><topic>Adhesion</topic><topic>Antibodies</topic><topic>Bacteria</topic><topic>Bacterial Adhesion</topic><topic>Bacterial Toxins - metabolism</topic><topic>Biology and Life Sciences</topic><topic>Caco-2 Cells</topic><topic>Cells</topic><topic>Colonization</topic><topic>Colonization factor</topic><topic>Countries</topic><topic>Developing 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countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28531220</pmid><doi>10.1371/journal.pntd.0005586</doi><orcidid>https://orcid.org/0000-0002-2972-6978</orcidid><orcidid>https://orcid.org/0000-0002-1148-697X</orcidid><orcidid>https://orcid.org/0000-0003-1085-0589</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_1910461852 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Adhesins Adhesins, Bacterial - metabolism Adhesion Antibodies Bacteria Bacterial Adhesion Bacterial Toxins - metabolism Biology and Life Sciences Caco-2 Cells Cells Colonization Colonization factor Countries Developing countries Diabetes Diarrhea E coli Enterocytes Enterotoxigenic Escherichia coli - pathogenicity Enterotoxins Enterotoxins - metabolism Epithelial cells Epithelial Cells - microbiology Epithelium Escherichia coli Escherichia coli Proteins - metabolism Fimbriae, Bacterial - metabolism Funding Genes Genomes Grants Heat Host-Pathogen Interactions Humans In vitro methods and tests Infectious diseases Interactions Internal medicine Intestine Kidney diseases Laboratories LDCs Mannans Mannose Medicine Medicine and Health Sciences Molecules Monolayers Monomolecular films Mutagenesis Mutants Pathogenesis Pathogens Pili Plasmids Protein Transport Proteins Specificity Stem cells Thermal stability Toxins Transcription Tropical diseases Veterans Virulence Virulence (Microbiology) |
| title | Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T04%3A12%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Highly%20conserved%20type%201%20pili%20promote%20enterotoxigenic%20E.%20coli%20pathogen-host%20interactions&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Sheikh,%20Alaullah&rft.date=2017-05-22&rft.volume=11&rft.issue=5&rft.spage=e0005586&rft.pages=e0005586-&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0005586&rft_dat=%3Cgale_plos_%3EA493733455%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1910461852&rft_id=info:pmid/28531220&rft_galeid=A493733455&rft_doaj_id=oai_doaj_org_article_20b9e7b27bac471fa50a59257d2aee30&rfr_iscdi=true |