Cpa, the Outer Membrane Protease of Cronobacter sakazakii, Activates Plasminogen and Mediates Resistance to Serum Bactericidal Activity
Cronobacter spp. are emerging neonatal pathogens in humans, associated with outbreaks of meningitis and sepsis. To cause disease, they must survive in blood and invade the central nervous system by penetrating the blood-brain barrier. C. sakazakii BAA-894 possesses an ~131-kb plasmid (pESA3) that en...
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description | Cronobacter spp. are emerging neonatal pathogens in humans, associated with outbreaks of meningitis and sepsis. To cause disease, they must survive in blood and invade the central nervous system by penetrating the blood-brain barrier. C. sakazakii BAA-894 possesses an ~131-kb plasmid (pESA3) that encodes an outer membrane protease (Cpa) that has significant identity to proteins that belong to the Pla subfamily of omptins. Members of this subfamily of proteins degrade a number of serum proteins, including circulating complement, providing protection from the complement-dependent serum killing. Moreover, proteins of the Pla subfamily can cause uncontrolled plasmin activity by converting plasminogen to plasmin and inactivating the plasmin inhibitor α2-antiplasmin (α2-AP). These reactions enhance the spread and invasion of bacteria in the host. In this study, we found that an isogenic cpa mutant showed reduced resistance to serum in comparison to its parent C. sakazakii BAA-894 strain. Overexpression of Cpa in C. sakazakii or Escherichia coli DH5α showed that Cpa proteolytically cleaved complement components C3, C3a, and C4b. Furthermore, a strain of C. sakazakii overexpressing Cpa caused a rapid activation of plasminogen and inactivation of α2-AP. These results strongly suggest that Cpa may be an important virulence factor involved in serum resistance, as well as in the spread and invasion of C. sakazakii. |
doi_str_mv | 10.1128/IAI.01165-10 |
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A.</contributor><creatorcontrib>Franco, A.A ; Kothary, M.H ; Gopinath, G ; Jarvis, K.G ; Grim, C.J ; Hu, L ; Datta, A.R ; McCardell, B.A ; Tall, B.D ; McCormick, B. A.</creatorcontrib><description>Cronobacter spp. are emerging neonatal pathogens in humans, associated with outbreaks of meningitis and sepsis. To cause disease, they must survive in blood and invade the central nervous system by penetrating the blood-brain barrier. C. sakazakii BAA-894 possesses an ~131-kb plasmid (pESA3) that encodes an outer membrane protease (Cpa) that has significant identity to proteins that belong to the Pla subfamily of omptins. Members of this subfamily of proteins degrade a number of serum proteins, including circulating complement, providing protection from the complement-dependent serum killing. Moreover, proteins of the Pla subfamily can cause uncontrolled plasmin activity by converting plasminogen to plasmin and inactivating the plasmin inhibitor α2-antiplasmin (α2-AP). These reactions enhance the spread and invasion of bacteria in the host. In this study, we found that an isogenic cpa mutant showed reduced resistance to serum in comparison to its parent C. sakazakii BAA-894 strain. Overexpression of Cpa in C. sakazakii or Escherichia coli DH5α showed that Cpa proteolytically cleaved complement components C3, C3a, and C4b. Furthermore, a strain of C. sakazakii overexpressing Cpa caused a rapid activation of plasminogen and inactivation of α2-AP. These results strongly suggest that Cpa may be an important virulence factor involved in serum resistance, as well as in the spread and invasion of C. sakazakii.</description><identifier>ISSN: 0019-9567</identifier><identifier>EISSN: 1098-5522</identifier><identifier>DOI: 10.1128/IAI.01165-10</identifier><identifier>PMID: 21245266</identifier><identifier>CODEN: INFIBR</identifier><language>eng</language><publisher>Washington, DC: American Society for Microbiology</publisher><subject>Amino Acid Sequence ; antibacterial properties ; bacteria ; Bacterial Infections ; Base Sequence ; Biological and medical sciences ; Blood Bactericidal Activity - immunology ; blood proteins ; blood serum ; blood-brain barrier ; central nervous system ; complement ; Complement System Proteins - immunology ; Complement System Proteins - metabolism ; Cronobacter sakazakii ; Cronobacter sakazakii - enzymology ; Cronobacter sakazakii - immunology ; Escherichia coli ; Fundamental and applied biological sciences. Psychology ; Humans ; immune evasion ; Immunoblotting ; meningitis ; Microbiology ; Molecular Sequence Data ; mutants ; pathogens ; Phylogeny ; plasmids ; plasmin ; plasminogen ; Plasminogen - immunology ; Plasminogen - metabolism ; Plasminogen Activators - genetics ; Plasminogen Activators - immunology ; Plasminogen Activators - metabolism ; Polymerase Chain Reaction ; Sequence Analysis, Protein ; Serine Endopeptidases - genetics ; Serine Endopeptidases - immunology ; Serine Endopeptidases - metabolism ; virulence ; Virulence Factors - genetics ; Virulence Factors - immunology ; Virulence Factors - metabolism</subject><ispartof>Infection and Immunity, 2011-04, Vol.79 (4), p.1578-1587</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011, American Society for Microbiology 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-1456fa775b21deade3a530766ed09cdfcdd3236afc0213e9b664db2dd0a8f083</citedby><cites>FETCH-LOGICAL-c468t-1456fa775b21deade3a530766ed09cdfcdd3236afc0213e9b664db2dd0a8f083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067567/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067567/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,729,782,786,887,3192,3193,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23982189$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21245266$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>McCormick, B. A.</contributor><creatorcontrib>Franco, A.A</creatorcontrib><creatorcontrib>Kothary, M.H</creatorcontrib><creatorcontrib>Gopinath, G</creatorcontrib><creatorcontrib>Jarvis, K.G</creatorcontrib><creatorcontrib>Grim, C.J</creatorcontrib><creatorcontrib>Hu, L</creatorcontrib><creatorcontrib>Datta, A.R</creatorcontrib><creatorcontrib>McCardell, B.A</creatorcontrib><creatorcontrib>Tall, B.D</creatorcontrib><title>Cpa, the Outer Membrane Protease of Cronobacter sakazakii, Activates Plasminogen and Mediates Resistance to Serum Bactericidal Activity</title><title>Infection and Immunity</title><addtitle>Infect Immun</addtitle><description>Cronobacter spp. are emerging neonatal pathogens in humans, associated with outbreaks of meningitis and sepsis. To cause disease, they must survive in blood and invade the central nervous system by penetrating the blood-brain barrier. C. sakazakii BAA-894 possesses an ~131-kb plasmid (pESA3) that encodes an outer membrane protease (Cpa) that has significant identity to proteins that belong to the Pla subfamily of omptins. Members of this subfamily of proteins degrade a number of serum proteins, including circulating complement, providing protection from the complement-dependent serum killing. Moreover, proteins of the Pla subfamily can cause uncontrolled plasmin activity by converting plasminogen to plasmin and inactivating the plasmin inhibitor α2-antiplasmin (α2-AP). These reactions enhance the spread and invasion of bacteria in the host. In this study, we found that an isogenic cpa mutant showed reduced resistance to serum in comparison to its parent C. sakazakii BAA-894 strain. Overexpression of Cpa in C. sakazakii or Escherichia coli DH5α showed that Cpa proteolytically cleaved complement components C3, C3a, and C4b. Furthermore, a strain of C. sakazakii overexpressing Cpa caused a rapid activation of plasminogen and inactivation of α2-AP. These results strongly suggest that Cpa may be an important virulence factor involved in serum resistance, as well as in the spread and invasion of C. sakazakii.</description><subject>Amino Acid Sequence</subject><subject>antibacterial properties</subject><subject>bacteria</subject><subject>Bacterial Infections</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blood Bactericidal Activity - immunology</subject><subject>blood proteins</subject><subject>blood serum</subject><subject>blood-brain barrier</subject><subject>central nervous system</subject><subject>complement</subject><subject>Complement System Proteins - immunology</subject><subject>Complement System Proteins - metabolism</subject><subject>Cronobacter sakazakii</subject><subject>Cronobacter sakazakii - enzymology</subject><subject>Cronobacter sakazakii - immunology</subject><subject>Escherichia coli</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>immune evasion</subject><subject>Immunoblotting</subject><subject>meningitis</subject><subject>Microbiology</subject><subject>Molecular Sequence Data</subject><subject>mutants</subject><subject>pathogens</subject><subject>Phylogeny</subject><subject>plasmids</subject><subject>plasmin</subject><subject>plasminogen</subject><subject>Plasminogen - immunology</subject><subject>Plasminogen - metabolism</subject><subject>Plasminogen Activators - genetics</subject><subject>Plasminogen Activators - immunology</subject><subject>Plasminogen Activators - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Sequence Analysis, Protein</subject><subject>Serine Endopeptidases - genetics</subject><subject>Serine Endopeptidases - immunology</subject><subject>Serine Endopeptidases - metabolism</subject><subject>virulence</subject><subject>Virulence Factors - genetics</subject><subject>Virulence Factors - immunology</subject><subject>Virulence Factors - metabolism</subject><issn>0019-9567</issn><issn>1098-5522</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkk1v1DAQhiMEotvCjTOYA-KyKbaTOM4FaVnxsVJRK1rO1sSe7Jom8db2tip_gL-N94MCJ8ueR4_teSfLXjB6yhiX7xazxSllTFQ5o4-yCaONzKuK88fZhFLW5E0l6qPsOIQfaVuWpXyaHXHGy4oLMcl-zdcwJXGF5HwT0ZOvOLQeRiQX3kWEgMR1ZO7d6FrQWyDANfyEa2unZKajvYWIgVz0EAY7uiWOBEaTLMbuCt8w2BBh1EiiI5foNwP5sBNZbQ30e4eN98-yJx30AZ8f1pPs6tPHq_mX_Oz882I-O8t1KWTMWVmJDuq6ajkzCAYLqApaC4GGNtp02piCFwI6TTkrsGmFKE3LjaEgOyqLk-z9XrvetAMajWP00Ku1twP4e-XAqv8ro12ppbtVBRV1amQSvD0IvLvZYIhqsEFj36eeuU1QspJcViUViZzuSe1dCB67h1sYVdvkVEpO7ZJLJwl_-e_LHuA_USXgzQGAoKHvUkrahr9c0UjOZJO413tuZZerO-tRpWyUTT-rG1UqVtXbNrzaMx04BUufPN8veRqPNCKSMVoXvwFpubhF</recordid><startdate>20110401</startdate><enddate>20110401</enddate><creator>Franco, A.A</creator><creator>Kothary, M.H</creator><creator>Gopinath, G</creator><creator>Jarvis, K.G</creator><creator>Grim, C.J</creator><creator>Hu, L</creator><creator>Datta, A.R</creator><creator>McCardell, B.A</creator><creator>Tall, B.D</creator><general>American Society for Microbiology</general><general>American Society for Microbiology (ASM)</general><scope>FBQ</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110401</creationdate><title>Cpa, the Outer Membrane Protease of Cronobacter sakazakii, Activates Plasminogen and Mediates Resistance to Serum Bactericidal Activity</title><author>Franco, A.A ; Kothary, M.H ; Gopinath, G ; Jarvis, K.G ; Grim, C.J ; Hu, L ; Datta, A.R ; McCardell, B.A ; Tall, B.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-1456fa775b21deade3a530766ed09cdfcdd3236afc0213e9b664db2dd0a8f083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Amino Acid Sequence</topic><topic>antibacterial properties</topic><topic>bacteria</topic><topic>Bacterial Infections</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Blood Bactericidal Activity - immunology</topic><topic>blood proteins</topic><topic>blood serum</topic><topic>blood-brain barrier</topic><topic>central nervous system</topic><topic>complement</topic><topic>Complement System Proteins - immunology</topic><topic>Complement System Proteins - metabolism</topic><topic>Cronobacter sakazakii</topic><topic>Cronobacter sakazakii - enzymology</topic><topic>Cronobacter sakazakii - immunology</topic><topic>Escherichia coli</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>immune evasion</topic><topic>Immunoblotting</topic><topic>meningitis</topic><topic>Microbiology</topic><topic>Molecular Sequence Data</topic><topic>mutants</topic><topic>pathogens</topic><topic>Phylogeny</topic><topic>plasmids</topic><topic>plasmin</topic><topic>plasminogen</topic><topic>Plasminogen - immunology</topic><topic>Plasminogen - metabolism</topic><topic>Plasminogen Activators - genetics</topic><topic>Plasminogen Activators - immunology</topic><topic>Plasminogen Activators - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>Sequence Analysis, Protein</topic><topic>Serine Endopeptidases - genetics</topic><topic>Serine Endopeptidases - immunology</topic><topic>Serine Endopeptidases - metabolism</topic><topic>virulence</topic><topic>Virulence Factors - genetics</topic><topic>Virulence Factors - immunology</topic><topic>Virulence Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Franco, A.A</creatorcontrib><creatorcontrib>Kothary, M.H</creatorcontrib><creatorcontrib>Gopinath, G</creatorcontrib><creatorcontrib>Jarvis, K.G</creatorcontrib><creatorcontrib>Grim, C.J</creatorcontrib><creatorcontrib>Hu, L</creatorcontrib><creatorcontrib>Datta, A.R</creatorcontrib><creatorcontrib>McCardell, B.A</creatorcontrib><creatorcontrib>Tall, B.D</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Infection and Immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Franco, A.A</au><au>Kothary, M.H</au><au>Gopinath, G</au><au>Jarvis, K.G</au><au>Grim, C.J</au><au>Hu, L</au><au>Datta, A.R</au><au>McCardell, B.A</au><au>Tall, B.D</au><au>McCormick, B. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cpa, the Outer Membrane Protease of Cronobacter sakazakii, Activates Plasminogen and Mediates Resistance to Serum Bactericidal Activity</atitle><jtitle>Infection and Immunity</jtitle><addtitle>Infect Immun</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>79</volume><issue>4</issue><spage>1578</spage><epage>1587</epage><pages>1578-1587</pages><issn>0019-9567</issn><eissn>1098-5522</eissn><coden>INFIBR</coden><abstract>Cronobacter spp. are emerging neonatal pathogens in humans, associated with outbreaks of meningitis and sepsis. To cause disease, they must survive in blood and invade the central nervous system by penetrating the blood-brain barrier. C. sakazakii BAA-894 possesses an ~131-kb plasmid (pESA3) that encodes an outer membrane protease (Cpa) that has significant identity to proteins that belong to the Pla subfamily of omptins. Members of this subfamily of proteins degrade a number of serum proteins, including circulating complement, providing protection from the complement-dependent serum killing. Moreover, proteins of the Pla subfamily can cause uncontrolled plasmin activity by converting plasminogen to plasmin and inactivating the plasmin inhibitor α2-antiplasmin (α2-AP). These reactions enhance the spread and invasion of bacteria in the host. In this study, we found that an isogenic cpa mutant showed reduced resistance to serum in comparison to its parent C. sakazakii BAA-894 strain. Overexpression of Cpa in C. sakazakii or Escherichia coli DH5α showed that Cpa proteolytically cleaved complement components C3, C3a, and C4b. Furthermore, a strain of C. sakazakii overexpressing Cpa caused a rapid activation of plasminogen and inactivation of α2-AP. These results strongly suggest that Cpa may be an important virulence factor involved in serum resistance, as well as in the spread and invasion of C. sakazakii.</abstract><cop>Washington, DC</cop><pub>American Society for Microbiology</pub><pmid>21245266</pmid><doi>10.1128/IAI.01165-10</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence antibacterial properties bacteria Bacterial Infections Base Sequence Biological and medical sciences Blood Bactericidal Activity - immunology blood proteins blood serum blood-brain barrier central nervous system complement Complement System Proteins - immunology Complement System Proteins - metabolism Cronobacter sakazakii Cronobacter sakazakii - enzymology Cronobacter sakazakii - immunology Escherichia coli Fundamental and applied biological sciences. Psychology Humans immune evasion Immunoblotting meningitis Microbiology Molecular Sequence Data mutants pathogens Phylogeny plasmids plasmin plasminogen Plasminogen - immunology Plasminogen - metabolism Plasminogen Activators - genetics Plasminogen Activators - immunology Plasminogen Activators - metabolism Polymerase Chain Reaction Sequence Analysis, Protein Serine Endopeptidases - genetics Serine Endopeptidases - immunology Serine Endopeptidases - metabolism virulence Virulence Factors - genetics Virulence Factors - immunology Virulence Factors - metabolism |
title | Cpa, the Outer Membrane Protease of Cronobacter sakazakii, Activates Plasminogen and Mediates Resistance to Serum Bactericidal Activity |
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