Glycosaminoglycan Binding Facilitates Entry of a Bacterial Pathogen into Central Nervous Systems

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Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications.

Vyšlo v časopise: Glycosaminoglycan Binding Facilitates Entry of a Bacterial Pathogen into Central Nervous Systems. PLoS Pathog 7(6): e32767. doi:10.1371/journal.ppat.1002082
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002082

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Zdroje

1. OrganizationWH 2004 The World Health Report 2004: changing history

2. EdwardsMSRenchMAHaffarAAMurphyMADesmondMM 1985 Long-term sequelae of group B streptococcal meningitis in infants. J Pediatr 106 717 722

3. StevensJPEamesMKentAHalketSHoltD 2003 Long term outcome of neonatal meningitis. Arch Dis Child Fetal Neonatal Ed 88 F179 184

4. GalizaEPHeathPT 2009 Improving the outcome of neonatal meningitis. Curr Opin Infect Dis 22 229 234

5. BerardiALugliLRossiCChinaMCVellaniG 2010 Neonatal bacterial meningitis. Minerva Pediatr 62 51 54

6. SchwartzBSchuchatAOxtobyMJCochiSLHightowerA 1991 Invasive group B streptococcal disease in adults. A population-based study in metropolitan Atlanta. JAMA 266 1112 1114

7. PharesCRLynfieldRFarleyMMMohle-BoetaniJHarrisonLH 2008 Epidemiology of invasive group B streptococcal disease in the United States, 1999–2005. JAMA 299 2056 2065

8. SkoffTHFarleyMMPetitSCraigASSchaffnerW 2009 Increasing burden of invasive group B streptococcal disease in nonpregnant adults, 1990–2007. Clin Infect Dis 49 85 92

9. KimKS 2008 Mechanisms of microbial traversal of the blood-brain barrier. Nat Rev Microbiol 6 625 634

10. MaiseyHCDoranKSNizetV 2008 Recent advances in understanding the molecular basis of group B Streptococcus virulence. Expert Rev Mol Med 10 e27

11. BishopJRSchukszMEskoJD 2007 Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature 446 1030 1037

12. BernfieldMGotteMParkPWReizesOFitzgeraldML 1999 Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem 68 729 777

13. EskoJDLindahlU 2001 Molecular diversity of heparan sulfate. J Clin Invest 108 169 173

14. RostandKSEskoJD 1997 Microbial adherence to and invasion through proteoglycans. Infect Immun 65 1 8

15. BulowHEHobertO 2006 The molecular diversity of glycosaminoglycans shapes animal development. Annu Rev Cell Dev Biol 22 375 407

16. EskoJDSelleckSB 2002 Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem 71 435 471

17. LawrenceROlsonSKSteeleREWangLWarriorR 2008 Evolutionary differences in glycosaminoglycan fine structure detected by quantitative glycan reductive isotope labeling. J Biol Chem 283 33674 33684

18. NakatoHKimataK 2002 Heparan sulfate fine structure and specificity of proteoglycan functions. Biochim Biophys Acta 1573 312 318

19. NybakkenKPerrimonN 2002 Heparan sulfate proteoglycan modulation of developmental signaling in Drosophila. Biochim Biophys Acta 1573 280 291

20. ShiehMTWuDunnDMontgomeryRIEskoJDSpearPG 1992 Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans. J Cell Biol 116 1273 1281

21. WuDunnDSpearPG 1989 Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J Virol 63 52 58

22. PetheKAlonsoSBietFDeloguGBrennanMJ 2001 The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nature 412 190 194

23. Alvarez-DominguezCVazquez-BolandJACarrasco-MarinELopez-MatoPLeyva-CobianF 1997 Host cell heparan sulfate proteoglycans mediate attachment and entry of Listeria monocytogenes, and the listerial surface protein ActA is involved in heparan sulfate receptor recognition. Infect Immun 65 78 88

24. BolducGRBaronMJGravekampCLachenauerCSMadoffLC 2002 The alpha C protein mediates internalization of group B Streptococcus within human cervical epithelial cells. Cell Microbiol 4 751 758

25. BaronMJBolducGRGoldbergMBAuperinTCMadoffLC 2004 Alpha C protein of group B Streptococcus binds host cell surface glycosaminoglycan and enters cells by an actin-dependent mechanism. J Biol Chem 279 24714 24723

26. BaronMJFilmanDJPropheteGAHogleJMMadoffLC 2007 Identification of a glycosaminoglycan binding region of the alpha C protein that mediates entry of group B streptococci into host cells. J Biol Chem 282 10526 10536

27. KocksCChoJHNehmeNUlvilaJPearsonAM 2005 Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila. Cell 123 335 346

28. AyresJSFreitagNSchneiderDS 2008 Identification of Drosophila mutants altering defense of and endurance to Listeria monocytogenes infection. Genetics 178 1807 1815

29. StoltzDAOzerEATaftPJBarryMLiuL 2008 Drosophila are protected from Pseudomonas aeruginosa lethality by transgenic expression of paraoxonase-1. J Clin Invest 118 3123 3131

30. SibleyCDDuanKFischerCParkinsMDStoreyDG 2008 Discerning the complexity of community interactions using a Drosophila model of polymicrobial infections. PLoS Pathog 4 e1000184

31. BaronMJWongSLNybakkenKCareyVJMadoffLC 2009 Host glycosaminoglycan confers susceptibility to bacterial infection in Drosophila melanogaster. Infect Immun 77 860 866

32. ParkerRJAuldVJ 2006 Roles of glia in the Drosophila nervous system. Semin Cell Dev Biol 17 66 77

33. StorkTEngelenDKrudewigASiliesMBaintonRJ 2008 Organization and function of the blood-brain barrier in Drosophila. J Neurosci 28 587 597

34. MayerFMayerNChinnLPinsonneaultRLKroetzD 2009 Evolutionary conservation of vertebrate blood-brain barrier chemoprotective mechanisms in Drosophila. J Neurosci 29 3538 3550

35. EdwardsTNMeinertzhagenIA 2010 The functional organisation of glia in the adult brain of Drosophila and other insects. Prog Neurobiol 90 471 497

36. IzumikawaTEgusaNTaniguchiFSugaharaKKitagawaH 2006 Heparan sulfate polymerization in Drosophila. J Biol Chem 281 1929 1934

37. TakeiYOzawaYSatoMWatanabeATabataT 2004 Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans. Development 131 73 82

38. ToyodaHKinoshita-ToyodaAFoxBSelleckSB 2000 Structural analysis of glycosaminoglycans in animals bearing mutations in sugarless, sulfateless, and tout-velu. Drosophila homologues of vertebrate genes encoding glycosaminoglycan biosynthetic enzymes. J Biol Chem 275 21856 21861

39. KimKS 2006 Microbial translocation of the blood-brain barrier. Int J Parasitol 36 607 614

40. BobardtMDSalmonPWangLEskoJDGabuzdaD 2004 Contribution of proteoglycans to human immunodeficiency virus type 1 brain invasion. J Virol 78 6567 6584

41. FlorisSvan den BornJvan der PolSMDijkstraCDDe VriesHE 2003 Heparan sulfate proteoglycans modulate monocyte migration across cerebral endothelium. J Neuropathol Exp Neurol 62 780 790

42. KimCWGoldbergerOAGalloRLBernfieldM 1994 Members of the syndecan family of heparan sulfate proteoglycans are expressed in distinct cell-, tissue-, and development-specific patterns. Mol Biol Cell 5 797 805

43. LeongJMWangHMagounLFieldJAMorrisseyPE 1998 Different classes of proteoglycans contribute to the attachment of Borrelia burgdorferi to cultured endothelial and brain cells. Infect Immun 66 994 999

44. StickensDZakBMRougierNEskoJDWerbZ 2005 Mice deficient in Ext2 lack heparan sulfate and develop exostoses. Development 132 5055 5068

45. TenenbaumTSpellerbergBAdamRVogelMKimKS 2007 Streptococcus agalactiae invasion of human brain microvascular endothelial cells is promoted by the laminin-binding protein Lmb. Microbes Infect 9 714 720

46. MaiseyHCHenslerMNizetVDoranKS 2007 Group B streptococcal pilus proteins contribute to adherence to and invasion of brain microvascular endothelial cells. J Bacteriol 189 1464 1467

47. DoranKSEngelsonEJKhosraviAMaiseyHCFedtkeI 2005 Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid. J Clin Invest 115 2499 2507

48. van SorgeNMQuachDGurneyMASullamPMNizetV 2009 The group B streptococcal serine-rich repeat 1 glycoprotein mediates penetration of the blood-brain barrier. J Infect Dis 199 1479 1487

49. DoranKSLiuGYNizetV 2003 Group B streptococcal β-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis. J Clin Invest 112 736 744

50. McCormickCDuncanGGoutsosKTTufaroF 2000 The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate. Proc Natl Acad Sci U S A 97 668 673

51. SenayCLindTMugurumaKToneYKitagawaH 2000 The EXT1/EXT2 tumor suppressors: catalytic activities and role in heparan sulfate biosynthesis. EMBO Rep 1 282 286

52. KamimuraKKoyamaTHabuchiHUedaRMasuM 2006 Specific and flexible roles of heparan sulfate modifications in Drosophila FGF signaling. J Cell Biol 174 773 778

53. KamimuraKRhodesJMUedaRMcNeelyMShuklaD 2004 Regulation of Notch signaling by Drosophila heparan sulfate 3-O sulfotransferase. J Cell Biol 166 1069 1079

54. StanfordKIWangLCastagnolaJSongDBishopJR 2010 Heparan sulfate 2-O-sulfotransferase is required for triglyceride-rich lipoprotein clearance. J Biol Chem 285 286 294

55. SugayaNHabuchiHNagaiNAshikari-HadaSKimataK 2008 6-O-sulfation of heparan sulfate differentially regulates various fibroblast growth factor-dependent signalings in culture. J Biol Chem 283 10366 10376

56. TonnaerELHafmansTGVan KuppeveltTHSandersEAVerweijPE 2006 Involvement of glycosaminoglycans in the attachment of pneumococci to nasopharyngeal epithelial cells. Microbes Infect 8 316 322

57. de VriesFPColeRDankertJFroschMvan PuttenJP 1998 Neisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors. Mol Microbiol 27 1203 1212

58. Behling-KellyEVonderheidHKimKSCorbeilLBCzuprynskiCJ 2006 Roles of cellular activation and sulfated glycans in Haemophilus somnus adherence to bovine brain microvascular endothelial cells. Infect Immun 74 5311 5318

59. MenozziFDBischoffRFortEBrennanMJLochtC 1998 Molecular characterization of the mycobacterial heparin-binding hemagglutinin, a mycobacterial adhesin. Proc Natl Acad Sci U S A 95 12625 12630

60. PortugalMITodeschiniARde LimaCSSilvaCAMohana-BorgesR 2008 Characterization of two heparan sulphate-binding sites in the mycobacterial adhesin Hlp. BMC Microbiol 8 75

61. CapilaILinhardtRJ 2002 Heparin-protein interactions. Angew Chem Int Ed Engl 41 391 412

62. HilemanREFrommJRWeilerJMLinhardtRJ 1998 Glycosaminoglycan-protein interactions: definition of consensus sites in glycosaminoglycan binding proteins. Bioessays 20 156 167

63. PerriereNDemeusePGarciaEReginaADebrayM 2005 Puromycin-based purification of rat brain capillary endothelial cell cultures. Effect on the expression of blood-brain barrier-specific properties. J Neurochem 93 279 289

64. WangLFusterMSriramaraoPEskoJD 2005 Endothelial heparan sulfate deficiency impairs L-selectin -⁠ and chemokine-mediated neutrophil trafficking during inflammatory responses. Nat Immunol 6 902 910

65. FusterMMWangLCastagnolaJSikoraLReddiK 2007 Genetic alteration of endothelial heparan sulfate selectively inhibits tumor angiogenesis. J Cell Biol 177 539 549

66. SeppKJAuldVJ 2003 Reciprocal interactions between neurons and glia are required for Drosophila peripheral nervous system development. J Neurosci 23 8221 8230