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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Veröffentlicht in:Infection and Immunity 2011-04, Vol.79 (4), p.1578-1587
Hauptverfasser: 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
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container_end_page 1587
container_issue 4
container_start_page 1578
container_title Infection and Immunity
container_volume 79
creator 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
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.
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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. 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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. 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source American Society for Microbiology; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
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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