RtxA1-Induced Expression of the Small GTPase Rac2 Plays a Key Role in the Pathogenicity of Vibrio vulnificus
Infection with the human pathogen Vibrio vulnificus leads to the generation of reactive oxygen species (ROS) via NAD(P)H oxidase (Nox) in host cells. In the present study, we employed mutant V. vulnificus strains to identify an essential virulence factor responsible for this ROS generation. We found...
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Veröffentlicht in: | The Journal of infectious diseases 2010-01, Vol.201 (1), p.97-105 |
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creator | Chung, Kyoung-Jin Cho, Eun-Jin Kim, Mi Kwang Kim, Young Ran Kim, Seok-Ho Yang, Hee-Young Chung, Ki-Chul Lee, Shee Eun Rhee, Joon Haeng Choy, Hyon E. Lee, Tae-Hoon |
description | Infection with the human pathogen Vibrio vulnificus leads to the generation of reactive oxygen species (ROS) via NAD(P)H oxidase (Nox) in host cells. In the present study, we employed mutant V. vulnificus strains to identify an essential virulence factor responsible for this ROS generation. We found that repeats-in-toxin A1 (RtxA1) expressed by V. vulnificus acts via Nox1 to induce significant ROS generation in the intestine epithelial cells, which ultimately results in cell death. Furthermore, RtxA1 modulates the small GTPase Rac2, which is known to play an important role in the activation of Nox. When mice were infected by the oral method, in contrast with the wild-type bacteria, an RtxA1-deficient V. vulnificus mutant was unable to induce ROS generation within the intestine and failed to cause death. These findings strongly suggest that RtxA1-induced Rac2 expression is a critical step underlying the pathogenicity of V. vulnificus |
doi_str_mv | 10.1086/648612 |
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In the present study, we employed mutant V. vulnificus strains to identify an essential virulence factor responsible for this ROS generation. We found that repeats-in-toxin A1 (RtxA1) expressed by V. vulnificus acts via Nox1 to induce significant ROS generation in the intestine epithelial cells, which ultimately results in cell death. Furthermore, RtxA1 modulates the small GTPase Rac2, which is known to play an important role in the activation of Nox. When mice were infected by the oral method, in contrast with the wild-type bacteria, an RtxA1-deficient V. vulnificus mutant was unable to induce ROS generation within the intestine and failed to cause death. These findings strongly suggest that RtxA1-induced Rac2 expression is a critical step underlying the pathogenicity of V. vulnificus</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/648612</identifier><identifier>PMID: 19919301</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Oxford: The University of Chicago Press</publisher><subject>Animals ; Bacteria ; Bacterial Toxins - metabolism ; Bacteriology ; Biological and medical sciences ; Caco-2 Cells ; Cell death ; Cell lines ; Cytotoxicity ; Epithelial cells ; Epithelial Cells - microbiology ; Fundamental and applied biological sciences. Psychology ; Humans ; Infections ; Infectious diseases ; Intestinal Mucosa - microbiology ; Medical sciences ; Mice ; Microbiology ; Miscellaneous ; NADPH Oxidase 1 ; NADPH Oxidases ; Oxidases ; rac GTP-Binding Proteins - metabolism ; RAC2 GTP-Binding Protein ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Reverse transcriptase polymerase chain reaction ; Vibrio Infections - microbiology ; Vibrio vulnificus ; Vibrio vulnificus - metabolism ; Vibrio vulnificus - pathogenicity</subject><ispartof>The Journal of infectious diseases, 2010-01, Vol.201 (1), p.97-105</ispartof><rights>2009 Infectious Diseases Society of America</rights><rights>2010 by the Infectious Diseases Society of America 2010</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-50d3f821a91401d280c7cf86d2ec5fa72d2c360729f81de39a219fbbbb5e0cfc3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/27794385$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/27794385$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,4024,27923,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22337426$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19919301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chung, Kyoung-Jin</creatorcontrib><creatorcontrib>Cho, Eun-Jin</creatorcontrib><creatorcontrib>Kim, Mi Kwang</creatorcontrib><creatorcontrib>Kim, Young Ran</creatorcontrib><creatorcontrib>Kim, Seok-Ho</creatorcontrib><creatorcontrib>Yang, Hee-Young</creatorcontrib><creatorcontrib>Chung, Ki-Chul</creatorcontrib><creatorcontrib>Lee, Shee Eun</creatorcontrib><creatorcontrib>Rhee, Joon Haeng</creatorcontrib><creatorcontrib>Choy, Hyon E.</creatorcontrib><creatorcontrib>Lee, Tae-Hoon</creatorcontrib><title>RtxA1-Induced Expression of the Small GTPase Rac2 Plays a Key Role in the Pathogenicity of Vibrio vulnificus</title><title>The Journal of infectious diseases</title><addtitle>The Journal of Infectious Diseases</addtitle><addtitle>The Journal of Infectious Diseases</addtitle><description>Infection with the human pathogen Vibrio vulnificus leads to the generation of reactive oxygen species (ROS) via NAD(P)H oxidase (Nox) in host cells. In the present study, we employed mutant V. vulnificus strains to identify an essential virulence factor responsible for this ROS generation. We found that repeats-in-toxin A1 (RtxA1) expressed by V. vulnificus acts via Nox1 to induce significant ROS generation in the intestine epithelial cells, which ultimately results in cell death. Furthermore, RtxA1 modulates the small GTPase Rac2, which is known to play an important role in the activation of Nox. When mice were infected by the oral method, in contrast with the wild-type bacteria, an RtxA1-deficient V. vulnificus mutant was unable to induce ROS generation within the intestine and failed to cause death. These findings strongly suggest that RtxA1-induced Rac2 expression is a critical step underlying the pathogenicity of V. vulnificus</description><subject>Animals</subject><subject>Bacteria</subject><subject>Bacterial Toxins - metabolism</subject><subject>Bacteriology</subject><subject>Biological and medical sciences</subject><subject>Caco-2 Cells</subject><subject>Cell death</subject><subject>Cell lines</subject><subject>Cytotoxicity</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - microbiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Intestinal Mucosa - microbiology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>NADPH Oxidase 1</subject><subject>NADPH Oxidases</subject><subject>Oxidases</subject><subject>rac GTP-Binding Proteins - metabolism</subject><subject>RAC2 GTP-Binding Protein</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Reverse transcriptase polymerase chain reaction</subject><subject>Vibrio Infections - microbiology</subject><subject>Vibrio vulnificus</subject><subject>Vibrio vulnificus - metabolism</subject><subject>Vibrio vulnificus - pathogenicity</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90ctuEzEUBmALgWgo8AYgswBWA76Mb8uqLU3VSoQQLurGcjw2dXHGqT2Dkrdn2omaFXjjxf_5t3QOAC8x-oCR5B95LTkmj8AEMyoqzjF9DCYIEVJhqdQBeFbKDUKoplw8BQdYKawowhMQ593mCFfnbdNb18DTzTq7UkJqYfKwu3bw68rECM8WM1McnBtL4CyabYEGXrgtnKfoYGjv5cx01-mXa4MN3fbu-fewzCHBP31sgw-2L8_BE29icS929yH49ul0cTytLj-fnR8fXVa2JqyrGGqolwQbhWuEGyKRFdZL3hBnmTeCNMRSjgRRXuLGUWUIVn45HOaQ9ZYegvdj7zqn296VTq9CsS5G07rUFy0olVQwpQb57r-S4FoxJsQe2pxKyc7rdQ4rk7caI323AT1uYICvd439cuWaPduNfABvd8AUa6LPprWhPDhCKBU14YN7M7rUr__92avR3JQu5X2HEKqmkg15NeahdG7zkJv8W3MxTEBPf17pL1MiT9jVQv-gfwFrOq7C</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Chung, Kyoung-Jin</creator><creator>Cho, Eun-Jin</creator><creator>Kim, Mi Kwang</creator><creator>Kim, Young Ran</creator><creator>Kim, Seok-Ho</creator><creator>Yang, Hee-Young</creator><creator>Chung, Ki-Chul</creator><creator>Lee, Shee Eun</creator><creator>Rhee, Joon Haeng</creator><creator>Choy, Hyon E.</creator><creator>Lee, Tae-Hoon</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><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>7QL</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>20100101</creationdate><title>RtxA1-Induced Expression of the Small GTPase Rac2 Plays a Key Role in the Pathogenicity of Vibrio vulnificus</title><author>Chung, Kyoung-Jin ; Cho, Eun-Jin ; Kim, Mi Kwang ; Kim, Young Ran ; Kim, Seok-Ho ; Yang, Hee-Young ; Chung, Ki-Chul ; Lee, Shee Eun ; Rhee, Joon Haeng ; Choy, Hyon E. ; Lee, Tae-Hoon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c425t-50d3f821a91401d280c7cf86d2ec5fa72d2c360729f81de39a219fbbbb5e0cfc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Bacteria</topic><topic>Bacterial Toxins - metabolism</topic><topic>Bacteriology</topic><topic>Biological and medical sciences</topic><topic>Caco-2 Cells</topic><topic>Cell death</topic><topic>Cell lines</topic><topic>Cytotoxicity</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - microbiology</topic><topic>Fundamental and applied biological sciences. 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subjects | Animals Bacteria Bacterial Toxins - metabolism Bacteriology Biological and medical sciences Caco-2 Cells Cell death Cell lines Cytotoxicity Epithelial cells Epithelial Cells - microbiology Fundamental and applied biological sciences. Psychology Humans Infections Infectious diseases Intestinal Mucosa - microbiology Medical sciences Mice Microbiology Miscellaneous NADPH Oxidase 1 NADPH Oxidases Oxidases rac GTP-Binding Proteins - metabolism RAC2 GTP-Binding Protein Reactive oxygen species Reactive Oxygen Species - metabolism Reverse transcriptase polymerase chain reaction Vibrio Infections - microbiology Vibrio vulnificus Vibrio vulnificus - metabolism Vibrio vulnificus - pathogenicity |
title | RtxA1-Induced Expression of the Small GTPase Rac2 Plays a Key Role in the Pathogenicity of Vibrio vulnificus |
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