Dissecting Virulence: Systematic and Functional Analyses of a Pathogenicity Island
Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli, and the mouse pathogen Citrobacter rodentium (CR) possess th...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2004-03, Vol.101 (10), p.3597-3602 |
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| creator | Deng, Wanyin Puente, José L. Gruenheid, Samantha Li, Yuling Vallance, Bruce A. Vázquez, Alejandra Barba, Jeannette Ibarra, J. Antonio O'Donnell, Paul Metalnikov, Pavel Ashman, Keith Lee, Sansan Goode, David Pawson, Tony Finlay, B. Brett Falkow, Stanley |
| description | Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli, and the mouse pathogen Citrobacter rodentium (CR) possess the locus of enterocyte effacement (LEE) PAI. We systematically mutagenized all 41 CR LEE genes and functionally characterized these mutants in vitro and in a murine infection model. We identified 33 virulence factors, including two virulence regulators and a hierarchical switch for type III secretion. In addition, 7 potential type III effectors encoded outside the LEE were identified by using a proteomics approach. These non-LEE effectors are encoded by three uncharacterized PAIs in EHEC O157, suggesting that these PAIs act cooperatively with the LEE in pathogenesis. Our findings provide significant insights into bacterial virulence mechanisms and disease. |
| doi_str_mv | 10.1073/pnas.0400326101 |
| format | Article |
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Antonio ; O'Donnell, Paul ; Metalnikov, Pavel ; Ashman, Keith ; Lee, Sansan ; Goode, David ; Pawson, Tony ; Finlay, B. Brett ; Falkow, Stanley</creator><creatorcontrib>Deng, Wanyin ; Puente, José L. ; Gruenheid, Samantha ; Li, Yuling ; Vallance, Bruce A. ; Vázquez, Alejandra ; Barba, Jeannette ; Ibarra, J. Antonio ; O'Donnell, Paul ; Metalnikov, Pavel ; Ashman, Keith ; Lee, Sansan ; Goode, David ; Pawson, Tony ; Finlay, B. Brett ; Falkow, Stanley</creatorcontrib><description>Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli, and the mouse pathogen Citrobacter rodentium (CR) possess the locus of enterocyte effacement (LEE) PAI. We systematically mutagenized all 41 CR LEE genes and functionally characterized these mutants in vitro and in a murine infection model. We identified 33 virulence factors, including two virulence regulators and a hierarchical switch for type III secretion. In addition, 7 potential type III effectors encoded outside the LEE were identified by using a proteomics approach. These non-LEE effectors are encoded by three uncharacterized PAIs in EHEC O157, suggesting that these PAIs act cooperatively with the LEE in pathogenesis. Our findings provide significant insights into bacterial virulence mechanisms and disease.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0400326101</identifier><identifier>PMID: 14988506</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Bacteria ; Biological Sciences ; Citrobacter rodentium ; Citrobacter rodentium - genetics ; Citrobacter rodentium - pathogenicity ; Disease ; Enterobacteriaceae Infections - etiology ; Enterobacteriaceae Infections - microbiology ; Escherichia coli ; Escherichia coli - genetics ; Escherichia coli - pathogenicity ; Gene expression regulation ; Gene Expression Regulation, Bacterial ; Genes ; Genes, Bacterial ; Genomes ; Genomic Islands ; Humans ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Microbiology ; Mutation ; pathogenicity islands ; Pathogens ; Plasmids ; Regulator genes ; Secretion ; Transcriptional regulatory elements ; Virulence ; Virulence - genetics ; Virulence factors ; Virulence Factors - genetics</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2004-03, Vol.101 (10), p.3597-3602</ispartof><rights>Copyright 1993/2004 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Mar 9, 2004</rights><rights>Copyright © 2004, The National Academy of Sciences 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-67f77dbb79bf5d1755ba8822f735b33d05bc9fdc8dac34834d1d71a9dfa48a793</citedby><cites>FETCH-LOGICAL-c526t-67f77dbb79bf5d1755ba8822f735b33d05bc9fdc8dac34834d1d71a9dfa48a793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/101/10.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3371525$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3371525$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14988506$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Deng, Wanyin</creatorcontrib><creatorcontrib>Puente, José L.</creatorcontrib><creatorcontrib>Gruenheid, Samantha</creatorcontrib><creatorcontrib>Li, Yuling</creatorcontrib><creatorcontrib>Vallance, Bruce A.</creatorcontrib><creatorcontrib>Vázquez, Alejandra</creatorcontrib><creatorcontrib>Barba, Jeannette</creatorcontrib><creatorcontrib>Ibarra, J. Antonio</creatorcontrib><creatorcontrib>O'Donnell, Paul</creatorcontrib><creatorcontrib>Metalnikov, Pavel</creatorcontrib><creatorcontrib>Ashman, Keith</creatorcontrib><creatorcontrib>Lee, Sansan</creatorcontrib><creatorcontrib>Goode, David</creatorcontrib><creatorcontrib>Pawson, Tony</creatorcontrib><creatorcontrib>Finlay, B. Brett</creatorcontrib><creatorcontrib>Falkow, Stanley</creatorcontrib><title>Dissecting Virulence: Systematic and Functional Analyses of a Pathogenicity Island</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli, and the mouse pathogen Citrobacter rodentium (CR) possess the locus of enterocyte effacement (LEE) PAI. We systematically mutagenized all 41 CR LEE genes and functionally characterized these mutants in vitro and in a murine infection model. We identified 33 virulence factors, including two virulence regulators and a hierarchical switch for type III secretion. In addition, 7 potential type III effectors encoded outside the LEE were identified by using a proteomics approach. These non-LEE effectors are encoded by three uncharacterized PAIs in EHEC O157, suggesting that these PAIs act cooperatively with the LEE in pathogenesis. Our findings provide significant insights into bacterial virulence mechanisms and disease.</description><subject>Animals</subject><subject>Bacteria</subject><subject>Biological Sciences</subject><subject>Citrobacter rodentium</subject><subject>Citrobacter rodentium - genetics</subject><subject>Citrobacter rodentium - pathogenicity</subject><subject>Disease</subject><subject>Enterobacteriaceae Infections - etiology</subject><subject>Enterobacteriaceae Infections - microbiology</subject><subject>Escherichia coli</subject><subject>Escherichia coli - genetics</subject><subject>Escherichia coli - pathogenicity</subject><subject>Gene expression regulation</subject><subject>Gene Expression Regulation, Bacterial</subject><subject>Genes</subject><subject>Genes, Bacterial</subject><subject>Genomes</subject><subject>Genomic Islands</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Microbiology</subject><subject>Mutation</subject><subject>pathogenicity islands</subject><subject>Pathogens</subject><subject>Plasmids</subject><subject>Regulator genes</subject><subject>Secretion</subject><subject>Transcriptional regulatory elements</subject><subject>Virulence</subject><subject>Virulence - genetics</subject><subject>Virulence factors</subject><subject>Virulence Factors - genetics</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90c9vFCEUB3BiNHZdPXsxOvFgvEz7gGEAEw9NtdqkicZfV8IAs2UzC9uBMe5_L5PddNWDFzjw-T4ePISeYjjFwOnZNuh0Cg0AJS0GfA8tMEhct42E-2gBQHgtGtKcoEcprQFAMgEP0QlupBAM2gX68s6n5Ez2YVX98OM0uGDcm-rrLmW30dmbSgdbXU6hkBj0UJ2XZZdcqmJf6eqzzjdx5YI3Pu-qqzQU_Rg96PWQ3JPDvkTfL99_u_hYX3_6cHVxfl0bRtpct7zn3HYdl13PLOaMdVoIQnpOWUepBdYZ2VsjrDa0EbSx2HKspe11IzSXdIne7utup27jrHEhj3pQ29Fv9LhTUXv190nwN2oVfypabgBR8q8O-THeTi5ltfHJuKG8wcUpKcyFENCSAl_-A9dxGss_JEUA05bN6xKd7ZEZY0qj6-8awaDmWal5Vuo4q5J4_mf_R38YTgGvD2BOHsvhuSRlkqt-GobsfuVCX_yfFvFsL9Ypx_GOUMoxI4z-BqSdsts</recordid><startdate>20040309</startdate><enddate>20040309</enddate><creator>Deng, Wanyin</creator><creator>Puente, José L.</creator><creator>Gruenheid, Samantha</creator><creator>Li, Yuling</creator><creator>Vallance, Bruce A.</creator><creator>Vázquez, Alejandra</creator><creator>Barba, Jeannette</creator><creator>Ibarra, J. 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Antonio</au><au>O'Donnell, Paul</au><au>Metalnikov, Pavel</au><au>Ashman, Keith</au><au>Lee, Sansan</au><au>Goode, David</au><au>Pawson, Tony</au><au>Finlay, B. Brett</au><au>Falkow, Stanley</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dissecting Virulence: Systematic and Functional Analyses of a Pathogenicity Island</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2004-03-09</date><risdate>2004</risdate><volume>101</volume><issue>10</issue><spage>3597</spage><epage>3602</epage><pages>3597-3602</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli, and the mouse pathogen Citrobacter rodentium (CR) possess the locus of enterocyte effacement (LEE) PAI. We systematically mutagenized all 41 CR LEE genes and functionally characterized these mutants in vitro and in a murine infection model. We identified 33 virulence factors, including two virulence regulators and a hierarchical switch for type III secretion. In addition, 7 potential type III effectors encoded outside the LEE were identified by using a proteomics approach. These non-LEE effectors are encoded by three uncharacterized PAIs in EHEC O157, suggesting that these PAIs act cooperatively with the LEE in pathogenesis. Our findings provide significant insights into bacterial virulence mechanisms and disease.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>14988506</pmid><doi>10.1073/pnas.0400326101</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bacteria Biological Sciences Citrobacter rodentium Citrobacter rodentium - genetics Citrobacter rodentium - pathogenicity Disease Enterobacteriaceae Infections - etiology Enterobacteriaceae Infections - microbiology Escherichia coli Escherichia coli - genetics Escherichia coli - pathogenicity Gene expression regulation Gene Expression Regulation, Bacterial Genes Genes, Bacterial Genomes Genomic Islands Humans Mice Mice, Inbred C3H Mice, Inbred C57BL Microbiology Mutation pathogenicity islands Pathogens Plasmids Regulator genes Secretion Transcriptional regulatory elements Virulence Virulence - genetics Virulence factors Virulence Factors - genetics |
| title | Dissecting Virulence: Systematic and Functional Analyses of a Pathogenicity Island |
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