Mucosal Reactive Oxygen Species Decrease Virulence by Disrupting Campylobacter jejuni Phosphotyrosine Signaling
Reactive oxygen species (ROS) play key roles in mucosal defense, yet how they are induced and the consequences for pathogens are unclear. We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by a...
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| Veröffentlicht in: | Cell host & microbe 2012-07, Vol.12 (1), p.47-59 |
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| creator | Corcionivoschi, Nicolae Alvarez, Luis A.J. Sharp, Thomas H. Strengert, Monika Alemka, Abofu Mantell, Judith Verkade, Paul Knaus, Ulla G. Bourke, Billy |
| description | Reactive oxygen species (ROS) play key roles in mucosal defense, yet how they are induced and the consequences for pathogens are unclear. We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by altering bacterial signal transduction. Upon C. jejuni invasion, ROS released from the intestinal mucosa inhibit the bacterial phosphotyrosine network that is regulated by the outer-membrane tyrosine kinase Cjtk (Cj1170/OMP50). ROS-mediated Cjtk inactivation results in an overall decrease in the phosphorylation of C. jejuni outer-membrane/periplasmic proteins, including UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme required for N-glycosylation and capsule formation. Cjtk positively regulates Gne by phosphorylating an active site tyrosine, while loss of Cjtk or ROS treatment inhibits Gne activity, causing altered polysaccharide synthesis. Thus, epithelial NADPH oxidases are an early antibacterial defense system in the intestinal mucosa that modifies virulence by disrupting bacterial signaling.
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► Campylobacter jejuni infection triggers epithelial NADPH oxidase activation ► Mucosal H2O2 inhibits phosphotyrosine signaling in extracellular C. jejuni ► The C. jejuni tyrosine kinase Cjtk is required for carbohydrate biosynthesis ► Mucosal ROS and disruption of Cjtk signaling attenuates pathogenicity |
| doi_str_mv | 10.1016/j.chom.2012.05.018 |
| format | Article |
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► Campylobacter jejuni infection triggers epithelial NADPH oxidase activation ► Mucosal H2O2 inhibits phosphotyrosine signaling in extracellular C. jejuni ► The C. jejuni tyrosine kinase Cjtk is required for carbohydrate biosynthesis ► Mucosal ROS and disruption of Cjtk signaling attenuates pathogenicity</description><identifier>ISSN: 1931-3128</identifier><identifier>EISSN: 1934-6069</identifier><identifier>DOI: 10.1016/j.chom.2012.05.018</identifier><identifier>PMID: 22817987</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amino Acid Sequence ; Bacterial Outer Membrane Proteins - metabolism ; Campylobacter jejuni - drug effects ; Campylobacter jejuni - metabolism ; Campylobacter jejuni - pathogenicity ; Catalytic Domain ; Dual Oxidases ; Epithelial Cells - metabolism ; Epithelial Cells - microbiology ; Host-Pathogen Interactions ; Humans ; Hydrogen Peroxide - metabolism ; Hydrogen Peroxide - pharmacology ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - microbiology ; Molecular Sequence Data ; NADPH Oxidase 1 ; NADPH Oxidases - metabolism ; Organ Culture Techniques ; Phosphotyrosine - metabolism ; Protein-Tyrosine Kinases - metabolism ; Reactive Oxygen Species - metabolism ; Signal Transduction ; UDPglucose 4-Epimerase - metabolism</subject><ispartof>Cell host & microbe, 2012-07, Vol.12 (1), p.47-59</ispartof><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-13c48047cb00215bc25b4c3f1f01c1d03a8c2f5c596e7917c3b79c94ef44da4b3</citedby><cites>FETCH-LOGICAL-c455t-13c48047cb00215bc25b4c3f1f01c1d03a8c2f5c596e7917c3b79c94ef44da4b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.chom.2012.05.018$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22817987$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Corcionivoschi, Nicolae</creatorcontrib><creatorcontrib>Alvarez, Luis A.J.</creatorcontrib><creatorcontrib>Sharp, Thomas H.</creatorcontrib><creatorcontrib>Strengert, Monika</creatorcontrib><creatorcontrib>Alemka, Abofu</creatorcontrib><creatorcontrib>Mantell, Judith</creatorcontrib><creatorcontrib>Verkade, Paul</creatorcontrib><creatorcontrib>Knaus, Ulla G.</creatorcontrib><creatorcontrib>Bourke, Billy</creatorcontrib><title>Mucosal Reactive Oxygen Species Decrease Virulence by Disrupting Campylobacter jejuni Phosphotyrosine Signaling</title><title>Cell host & microbe</title><addtitle>Cell Host Microbe</addtitle><description>Reactive oxygen species (ROS) play key roles in mucosal defense, yet how they are induced and the consequences for pathogens are unclear. We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by altering bacterial signal transduction. Upon C. jejuni invasion, ROS released from the intestinal mucosa inhibit the bacterial phosphotyrosine network that is regulated by the outer-membrane tyrosine kinase Cjtk (Cj1170/OMP50). ROS-mediated Cjtk inactivation results in an overall decrease in the phosphorylation of C. jejuni outer-membrane/periplasmic proteins, including UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme required for N-glycosylation and capsule formation. Cjtk positively regulates Gne by phosphorylating an active site tyrosine, while loss of Cjtk or ROS treatment inhibits Gne activity, causing altered polysaccharide synthesis. Thus, epithelial NADPH oxidases are an early antibacterial defense system in the intestinal mucosa that modifies virulence by disrupting bacterial signaling.
[Display omitted]
► Campylobacter jejuni infection triggers epithelial NADPH oxidase activation ► Mucosal H2O2 inhibits phosphotyrosine signaling in extracellular C. jejuni ► The C. jejuni tyrosine kinase Cjtk is required for carbohydrate biosynthesis ► Mucosal ROS and disruption of Cjtk signaling attenuates pathogenicity</description><subject>Amino Acid Sequence</subject><subject>Bacterial Outer Membrane Proteins - metabolism</subject><subject>Campylobacter jejuni - drug effects</subject><subject>Campylobacter jejuni - metabolism</subject><subject>Campylobacter jejuni - pathogenicity</subject><subject>Catalytic Domain</subject><subject>Dual Oxidases</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - microbiology</subject><subject>Host-Pathogen Interactions</subject><subject>Humans</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Intestinal Mucosa - drug effects</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - microbiology</subject><subject>Molecular Sequence Data</subject><subject>NADPH Oxidase 1</subject><subject>NADPH Oxidases - metabolism</subject><subject>Organ Culture Techniques</subject><subject>Phosphotyrosine - metabolism</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Signal Transduction</subject><subject>UDPglucose 4-Epimerase - metabolism</subject><issn>1931-3128</issn><issn>1934-6069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF-L1DAUxYMo7rr6BXyQfIHW3DSZtiCCzPoPVlZc9TWkt7czKZ2mJO1gv70ZRxd98eleuOecy_kx9hxEDgI2L_sc9_6QSwEyFzoXUD1gl1AXKtuITf3w1w5ZAbK6YE9i7IXQWpTwmF1IWUFZV-Ul858W9NEO_AtZnN2R-O2PdUcjv5sIHUV-TRjIRuLfXVgGGpF4s_JrF8MyzW7c8a09TOvgm2SnwHvql9Hxz3sfp72f1-CjG4nfud1ohyR_yh51doj07Pe8Yt_evf26_ZDd3L7_uH1zk6HSes6gQFUJVWIjhATdoNSNwqKDTgBCKwpboew06npDZQ0lFk1ZY62oU6q1qimu2Otz7rQ0B2qRxjnYwUzBHWxYjbfO_HsZ3d7s_NEUpao1QAqQ5wBMFWKg7t4Lwpzwm96c8JsTfiO0SfiT6cXfX-8tf3gnwauzgFL3o6NgYqKcoLYuEM6m9e5_-T8BnyqanA</recordid><startdate>20120719</startdate><enddate>20120719</enddate><creator>Corcionivoschi, Nicolae</creator><creator>Alvarez, Luis A.J.</creator><creator>Sharp, Thomas H.</creator><creator>Strengert, Monika</creator><creator>Alemka, Abofu</creator><creator>Mantell, Judith</creator><creator>Verkade, Paul</creator><creator>Knaus, Ulla G.</creator><creator>Bourke, Billy</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>5PM</scope></search><sort><creationdate>20120719</creationdate><title>Mucosal Reactive Oxygen Species Decrease Virulence by Disrupting Campylobacter jejuni Phosphotyrosine Signaling</title><author>Corcionivoschi, Nicolae ; 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We report that ROS generated by epithelial NADPH oxidases (Nox1/Duox2) during Campylobacter jejuni infection impair bacterial capsule formation and virulence by altering bacterial signal transduction. Upon C. jejuni invasion, ROS released from the intestinal mucosa inhibit the bacterial phosphotyrosine network that is regulated by the outer-membrane tyrosine kinase Cjtk (Cj1170/OMP50). ROS-mediated Cjtk inactivation results in an overall decrease in the phosphorylation of C. jejuni outer-membrane/periplasmic proteins, including UDP-GlcNAc/Glc 4-epimerase (Gne), an enzyme required for N-glycosylation and capsule formation. Cjtk positively regulates Gne by phosphorylating an active site tyrosine, while loss of Cjtk or ROS treatment inhibits Gne activity, causing altered polysaccharide synthesis. Thus, epithelial NADPH oxidases are an early antibacterial defense system in the intestinal mucosa that modifies virulence by disrupting bacterial signaling.
[Display omitted]
► Campylobacter jejuni infection triggers epithelial NADPH oxidase activation ► Mucosal H2O2 inhibits phosphotyrosine signaling in extracellular C. jejuni ► The C. jejuni tyrosine kinase Cjtk is required for carbohydrate biosynthesis ► Mucosal ROS and disruption of Cjtk signaling attenuates pathogenicity</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22817987</pmid><doi>10.1016/j.chom.2012.05.018</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Amino Acid Sequence Bacterial Outer Membrane Proteins - metabolism Campylobacter jejuni - drug effects Campylobacter jejuni - metabolism Campylobacter jejuni - pathogenicity Catalytic Domain Dual Oxidases Epithelial Cells - metabolism Epithelial Cells - microbiology Host-Pathogen Interactions Humans Hydrogen Peroxide - metabolism Hydrogen Peroxide - pharmacology Intestinal Mucosa - drug effects Intestinal Mucosa - metabolism Intestinal Mucosa - microbiology Molecular Sequence Data NADPH Oxidase 1 NADPH Oxidases - metabolism Organ Culture Techniques Phosphotyrosine - metabolism Protein-Tyrosine Kinases - metabolism Reactive Oxygen Species - metabolism Signal Transduction UDPglucose 4-Epimerase - metabolism |
| title | Mucosal Reactive Oxygen Species Decrease Virulence by Disrupting Campylobacter jejuni Phosphotyrosine Signaling |
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