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Group A Streptococcus Secreted Esterase Hydrolyzes Platelet-Activating Factor to Impede Neutrophil Recruitment and Facilitate Innate Immune Evasion

By Mengyao Liu, Hui Zhu, Jinquan Li, Cristiana C. Garcia, Wenchao Feng, Liliya N. Kirpotina, Jonathan Hilmer, Luciana P. Tavares, Arthur W. Layton, Mark T. Quinn, Brian Bothner, Mauro M. Teixeira and Benfang Lei

Abstract

The innate immune system is the first line of host defense against invading organisms. Thus, pathogens have developed virulence mechanisms to evade the innate immune system. Here, we report a novel means for inhibition of neutrophil recruitment by Group A Streptococcus (GAS). Deletion of the secreted esterase gene (designated sse) in M1T1 GAS strains with (MGAS5005) and without (MGAS2221) a null covS mutation enhances neutrophil ingress to infection sites in the skin of mice. In trans expression of SsE in MGAS2221 reduces neutrophil recruitment and enhances skin invasion. The sse deletion mutant of MGAS5005 (ΔsseMGAS5005) is more efficiently cleared from skin than the parent strain. SsE hydrolyzes the sn-2 ester bond of platelet-activating factor (PAF), converting biologically active PAF into inactive lyso-PAF. KM and kcat of SsE for hydrolysis of 2-thio-PAF were similar to those of the human plasma PAF acetylhydrolase. Treatment of PAF with SsE abolishes the capacity of PAF to induce activation and chemotaxis of human neutrophils. More importantly, PAF receptor-deficient mice significantly reduce neutrophil infiltration to the site of ΔsseMGAS5005 infection. These findings identify the first secreted PAF acetylhydrolase of bacterial pathogens and support a novel GAS evasion mechanism that reduces phagocyte recruitment to sites of infection by inactivating PAF, providing a new paradigm for bacterial evasion of neutrophil responses

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3320582
Provided by: PubMed Central

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Citations

  1. (2008). A chemokinedegrading extracellular protease made by group A Streptococcus alters pathogenesis by enhancing evasion of the innate immune response.
  2. (2011). A novel platelet-activating factor acetylhydrolase discovered in a metagenome from the earthworm-associated microbial community.
  3. (1999). A Response Regulator That Represses Transcription of Several Virulence Operons in the Group A Streptococcus.
  4. (2006). A streptococcal protease that degrades CXC chemokines and impairs bacterial clearance from infected tissues.
  5. (1999). A two-component regulatory system, CsrR-CsrS, represses expression of three Streptococcus pyogenes Targeting PAF for Innate Immune Evasion PLoS Pathogens
  6. (2008). A yeast PAF acetylhydrolase ortholog suppresses oxidative death.
  7. (1981). Activation of human neutrophils with 1-O-hexadecyl/octadecyl-2-acetyl-snglycerol-3-phosphorylcholine (platelet activating factor).
  8. (2007). Active and passive immunizations with the streptococcal esterase Sse protect mice against subcutaneous infection with group A streptococci.
  9. (1995). Anti-inflammatory properties of a platelet-activating factor acetylhydrolase.
  10. (2000). Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection.
  11. (2002). Bjo ¨rck L
  12. (1991). Catabolism of plateletactivating factor and its acyl analog. Differentiation of the activities of lysophospholipase and platelet-activating-factor acetylhydrolase.
  13. (1996). cDNA cloning and expression of intracellular platelet-activating factor (PAF) acetylhydrolase II: Its homology with plasma PAF acetylhydrolase.
  14. (2010). Chemokine-cleaving Streptococcus pyogenes protease SpyCEP is necessary and sufficient for bacterial dissemination within soft tissues and the respiratory tract.
  15. (1991). Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung.
  16. (2004). Contribution of CsrRregulated virulence factors to the progress and outcome of murine skin infections by Streptococcus pyogenes.
  17. (2005). Correlation of histopathologic findings with clinical outcome in necrotizing fasciitis.
  18. (2009). CovS simultaneously activates and inhibits the CovR-mediated repression of distinct subsets of group A Streptococcus virulence factor-encoding genes.
  19. (2005). Cytocidal effect of Streptococcus pyogenes on mouse neutrophils in vivo and the critical role of streptolysin S.
  20. (2007). DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection.
  21. (2008). Esterase SeE of Streptococcus equi ssp. equi is a novel nonspecific carboxylic ester hydrolase.
  22. (2001). Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis.
  23. (2006). GenomeWide Analysis of Group A Streptococci Reveals a Mutation That Modulates Global Phenotype and Disease Specificity.
  24. (2010). Highly frequent mutations in negative regulators of multiple virulence genes in group A streptococcal toxic shock syndrome isolates.
  25. (2010). Identification of novel small-molecule agonists for human formyl peptide receptors and pharmacophore models of their recognition.
  26. (1980). Identification of platelet activating factor isolated from rabbit basophils as acetyl glyceryl ether phosphorylcholine.
  27. (2009). Impact of immunization against SpyCEP during invasive disease with two streptococcal species: Streptococcus pyogenes and Streptococcus equi.
  28. (1998). Impaired anaphylactic responses with intact sensitivity to endotoxin in mice lacking a platelet-activating factor receptor.
  29. (2004). Improved host defense against pneumococcal pneumonia in platelet-activating factor receptor-deficient mice.
  30. (2005). Insights into pneumococcal pathogenesis from the crystal structure of the modular teichoic acid phosphorylcholine esterase Pce.
  31. (1997). Intranasal immunization with C5a peptidase prevents nasopharyngeal colonization of mice by the group A Streptococcus.
  32. (1992). Introduction of the emm6 gene into an emm-deleted strain of Streptococcus pyogenes restores its ability to resist phagocytosis.
  33. (2004). Invasive M1T1 group A Streptococcus undergoes a phase-shift in vivo to prevent proteolytic degradation of multiple virulence factors by SpeB.
  34. (1972). Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor.
  35. (1996). Mammalian platelet-activating factor acetylhydrolases.
  36. (1982). Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker.
  37. (1985). Mechanism of action of the group A streptococcal C5a inactivator.
  38. (1999). Molecular, serological, and clinical features of 16 consecutive cases of invasive streptococcal disease.
  39. (2007). Neutrophil isolation from nonhuman species.
  40. (2002). Platelet-activating factor induces lung inflammation and leak in rats: hydrogen peroxide production along neutrophil-lung endothelial cell interfaces.
  41. (2008). Platelet-activating factor receptor contributes to host defense against Pseudomonas aeruginosa pneumonia but is not essential for the accompanying inflammatory and procoagulant response.
  42. (1993). Platelet-activating factor: receptors and signal transduction.
  43. (1997). Plateletactivating factor acetylhydrolases.
  44. (2004). Plateletactivating factor receptor-deficient mice show an unaltered clearance of nontypeable Haemophilus influenzae from their respiratory tract.
  45. (1998). Plateletactivating factor synthesized by IL-12-stimulated polymorphonuclear neutrophils and NK cells mediates chemotaxis.
  46. (1993). Plateletactivating factor: a phospholipid autacoid with diverse actions.
  47. (1993). Purification and characterization of bovine brain platelet-activating factor acetylhydrolase.
  48. (2009). Serum activity of plateletactivating factor acetylhydrolase is a potential clinical marker for leptospirosis pulmonary hemorrhage.
  49. (2006). Signaling via platelet-activating factor receptors accounts for the impairment of neutrophil migration in polymicrobial sepsis.
  50. (2005). Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes.
  51. (2001). Spontaneous mutations in the CsrRS two-component regulatory system of Streptococcus pyogenes result in enhanced virulence in a murine model of skin and soft tissue infection.
  52. (1999). Staging of the baboon response to group A streptococci administered intramuscularly: a descriptive study of the clinical symptoms and clinical chemical response patterns.
  53. (2009). Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosis.
  54. (2005). The global burden of group A streptococcal diseases.
  55. (2008). The IL-8 protease SpyCEP/ScpC of group A Streptococcus promotes resistance to neutrophil killing.
  56. (2010). The platelet activating factor (PAF) signaling cascade in systemic inflammatory responses.
  57. (2009). The secreted esterase of group a streptococcus is important for invasive skin infection and dissemination in mice.
  58. (2006). Trigger for group A streptococcal M1T1 invasive disease.

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