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Recent advances in understanding the molecular basis of group B Streptococcus virulence

  • Heather C. Maisey (a1), Kelly S. Doran (a2) and Victor Nizet (a1) (a3)
Abstract

Group B Streptococcus commonly colonises healthy adults without symptoms, yet under certain circumstances displays the ability to invade host tissues, evade immune detection and cause serious invasive disease. Consequently, Group B Streptococcus remains a leading cause of neonatal pneumonia, sepsis and meningitis. Here we review recent information on the bacterial factors and mechanisms that direct host–pathogen interactions involved in the pathogenesis of Group B Streptococcus infection. New research on host signalling and inflammatory responses to Group B Streptococcus infection is summarised. An understanding of the complex interplay between Group B Streptococcus and host provides valuable insight into pathogen evolution and highlights molecular targets for therapeutic intervention.

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Corresponding author
*Corresponding author: Victor Nizet, Professor of Pediatrics and Pharmacy, University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, 9500 Gilman Drive, La Jolla, CA 92093-0687, USA. Tel:  + 1 858 534 7408; Fax:  + 1 858 534 5611; E-mail: vnizet@ucsd.edu
References
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1Johri A.K. et al. (2006) Group B Streptococcus: global incidence and vaccine development. Nat Rev Microbiol 4, 932-942
2Edwards M.S. and Baker C.J. (2005) Group B streptococcal infections in elderly adults. Clin Infect Dis 41, 839-847
3Campbell J.R. et al. (2000) Group B streptococcal colonization and serotype-specific immunity in pregnant women at delivery. Obstet Gynecol 96, 498-503
4Beckmann C. et al. (2002) Identification of novel adhesins from Group B streptococci by use of phage display reveals that C5a peptidase mediates fibronectin binding. Infect Immun 70, 2869-2876
5Cheng Q. et al. (2002) The group B streptococcal C5a peptidase is both a specific protease and an invasin. Infect Immun 70, 2408-2413
6Brown C.K. et al. (2005) Structure of the streptococcal cell wall C5a peptidase. Proc Natl Acad Sci U S A 102, 18391-18396
7Cleary P.P. et al. (2004) Immunization with C5a peptidase from either group A or B streptococci enhances clearance of group A streptococci from intranasally infected mice. Vaccine 22, 4332-4341
8Tamura G.S. et al. (2006) High-affinity interaction between fibronectin and the group B streptococcal C5a peptidase is unaffected by a naturally occurring four-amino-acid deletion that eliminates peptidase activity. Infect Immun 74, 5739-5746
9Spellerberg B. et al. (1999) Lmb, a protein with similarities to the LraI adhesin family, mediates attachment of Streptococcus agalactiae to human laminin. Infect Immun 67, 871-878
10Schubert A. et al. (2004) The fibrinogen receptor FbsA promotes adherence of Streptococcus agalactiae to human epithelial cells. Infect Immun 72, 6197-6205
11Samen U. et al. (2007) The surface protein Srr-1 of Streptococcus agalactiae binds human keratin 4 and promotes adherence to epithelial HEp-2 cells. Infect Immun 75, 5405-5414
12Seepersaud R. et al. (2005) Characterization of a novel leucine-rich repeat protein antigen from group B streptococci that elicits protective immunity. Infect Immun 73, 1671-1683
13Lauer P. et al. (2005) Genome analysis reveals pili in Group B Streptococcus. Science 309, 105
14Sauer F.G. et al. (2000) Bacterial pili: molecular mechanisms of pathogenesis. Curr Opin Microbiol 3, 65-72
15Rosini R. et al. (2006) Identification of novel genomic islands coding for antigenic pilus-like structures in Streptococcus agalactiae. Mol Microbiol 61, 126-141
16Dramsi S. et al. (2006) Assembly and role of pili in group B streptococci. Mol Microbiol 60, 1401-1413
17Maisey H.C. et al. (2007) Group B streptococcal pilus proteins contribute to adherence to and invasion of brain microvascular endothelial cells. J Bacteriol 189, 1464-1467
18Krishnan V. et al. (2007) An IgG-like domain in the minor pilin GBS52 of Streptococcus agalactiae mediates lung epithelial cell adhesion. Structure 15, 893-903
19Galask R.P. et al. (1984) Bacterial attachment to the chorioamniotic membranes. Am J Obstet Gynecol 148, 915-928
20Winram S.B. et al. (1998) Characterization of group B streptococcal invasion of human chorion and amnion epithelial cells In vitro. Infect Immun 66, 4932-4941
21Lin B. et al. (1994) Cloning and expression of the gene for group B streptococcal hyaluronate lyase. J Biol Chem 269, 30113-30116
22Rubens C.E. et al. (1991) Pathophysiology and histopathology of group B streptococcal sepsis in Macaca nemestrina primates induced after intraamniotic inoculation: evidence for bacterial cellular invasion. J Infect Dis 164, 320-330
23Rubens C.E. et al. (1992) Respiratory epithelial cell invasion by group B streptococci. Infect Immun 60, 5157-5163
24Gibson R.L. et al. (1993) Group B streptococci invade endothelial cells: type III capsular polysaccharide attenuates invasion. Infect Immun 61, 478-485
25Valentin-Weigand P. et al. (1997) Characterization of group B streptococcal invasion in HEp-2 epithelial cells. FEMS Microbiol Lett 147, 69-74
26Nizet V. et al. (1997) Invasion of brain microvascular endothelial cells by group B streptococci. Infect Immun 65, 5074-5081
27Tenenbaum T. et al. (2007) Streptococcus agalactiae invasion of human brain microvascular endothelial cells is promoted by the laminin-binding protein Lmb. Microbes Infect 9, 714-720
28Adderson E.E. et al. (2003) Subtractive hybridization identifies a novel predicted protein mediating epithelial cell invasion by virulent serotype III group B Streptococcus agalactiae. Infect Immun 71, 6857-6863
29Bolduc G.R. et al. (2002) The alpha C protein mediates internalization of group B Streptococcus within human cervical epithelial cells. Cell Microbiol 4, 751-758
30Li J. et al. (1997) Inactivation of the alpha C protein antigen gene, bca, by a novel shuttle/suicide vector results in attenuation of virulence and immunity in group B Streptococcus. Proc Natl Acad Sci U S A 94, 13251-13256
31Baron M.J. et al. (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
32Baron M.J. et al. (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
33Bolduc G.R. and Madoff L.C. (2007) The group B streptococcal alpha C protein binds alpha1beta1-integrin through a novel KTD motif that promotes internalization of GBS within human epithelial cells. Microbiology 153, 4039-4049
34Dumenil G. and Nassif X. (2005) Extracellular bacterial pathogens and small GTPases of the Rho family: an unexpected combination. Curr Top Microbiol Immunol 291, 11-28
35Burnham C.A., Shokoples S.E. and Tyrrell G.J. (2007) Rac1, RhoA, and Cdc42 participate in HeLa cell invasion by group B streptococcus. FEMS Microbiol Lett 272, 8-14
36Wang Q.Q. et al. (2008) Integrin beta 1 regulates phagosome maturation in macrophages through Rac expression. J Immunol 180, 2419-2428
37Burnham C.A., Shokoples S.E. and Tyrrell G.J. (2007) Invasion of HeLa cells by group B streptococcus requires the phosphoinositide-3-kinase signalling pathway and modulates phosphorylation of host-cell Akt and glycogen synthase kinase-3. Microbiology 153, 4240-4252
38Nizet V. et al. (1996) Group B streptococcal β-hemolysin expression is associated with injury of lung epithelial cells. Infect Immun 64, 3818-3826
39Gibson R.L., Nizet V. and Rubens C.E. (1999) Group B streptococcal β-hemolysin promotes injury of lung microvascular endothelial cells. Pediatr Res 45, 626-634
40Doran K.S. et al. (2002) Group B streptococcal β-hemolysin/cytolysin promotes invasion of human lung epithelial cells and the release of interleukin-8. J Infect Dis 185, 196-203
41Hensler M.E. et al. (2005) Virulence role of group B Streptococcus β-hemolysin/cytolysin in a neonatal rabbit model of early-onset pulmonary infection. J Infect Dis 191, 1287-1291
42Terao Y. et al. (2006) Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils. J Biol Chem 281, 14215-14223
43Cole J.N. et al. (2006) Trigger for group A streptococcal M1T1 invasive disease. FASEB J 20, 1745-1747
44Seifert K.N. et al. (2003) Characterization of group B streptococcal glyceraldehyde-3-phosphate dehydrogenase: surface localization, enzymatic activity, and protein-protein interactions. Can J Microbiol 49, 350-356
45Magalhaes V. et al. (2007) Interaction with human plasminogen system turns on proteolytic activity in Streptococcus agalactiae and enhances its virulence in a mouse model. Microbes Infect 9, 1276-1284
46Soriani M. et al. (2006) Group B Streptococcus crosses human epithelial cells by a paracellular route. J Infect Dis 193, 241-250
47Maruvada R., Blom A.M. and Prasadarao N.V. (2008) Effects of complement regulators bound to Escherichia coli K1 and Group B Streptococcus on the interaction with host cells. Immunology 124, 265-276
48Jennings H.J. et al. (1983) Structure of native polysaccharide antigens of type Ia and type Ib group B Streptococcus. Biochemistry 22, 1258-1264
49Wessels M.R. et al. (1989) Isolation and characterization of type IV group B Streptococcus capsular polysaccharide. Infect Immun 57, 1089-1094
50Wessels M.R. et al. (1987) Structure and immunochemistry of an oligosaccharide repeating unit of the capsular polysaccharide of type III group B Streptococcus. A revised structure for the type III group B streptococcal polysaccharide antigen. J Biol Chem 262, 8262-8267
51Jennings H.J. et al. (1983) Structural determination of the capsular polysaccharide antigen of type II group B Streptococcus. J Biol Chem 258, 1793-1798
52Kogan G. et al. (1995) Structural elucidation of the novel type VII group B Streptococcus capsular polysaccharide by high resolution NMR spectroscopy. Carbohydr Res 277, 1-9
53Kogan G. et al. (1996) Structural and immunochemical characterization of the type VIII group B Streptococcus capsular polysaccharide. J Biol Chem 271, 8786-8790
54Slotved H.C. et al. (2007) Serotype IX, a proposed new Streptococcus agalactiae serotype. J Clin Microbiol 45, 2929-2936
55Campbell J.R., Baker C.J. and Edwards M.S. (1991) Deposition and degradation of C3 on type III group B streptococci. Infect Immun 59, 1978-1983
56Marques M.B. et al. (1992) Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III group B streptococci. Infect Immun 60, 3986-3993
57Segura M.A., Cleroux P. and Gottschalk M. (1998) Streptococcus suis and group B Streptococcus differ in their interactions with murine macrophages. FEMS Immunol Med Microbiol 21, 189-195
58Takahashi S. et al. (1999) Capsular sialic acid limits C5a production on type III group B streptococci. Infect Immun 67, 1866-1870
59Santi I. et al. (2007) BibA: a novel immunogenic bacterial adhesin contributing to group B Streptococcus survival in human blood. Mol Microbiol 63, 754-767
60Jarva H. et al. (2004) The group B streptococcal beta and pneumococcal Hic proteins are structurally related immune evasion molecules that bind the complement inhibitor factor H in an analogous fashion. J Immunol 172, 3111-3118
61Jerlstrom P.G., Chhatwal G.S. and Timmis K.N. (1991) The IgA-binding beta antigen of the c protein complex of Group B streptococci: sequence determination of its gene and detection of two binding regions. Mol Microbiol 5, 843-849
62Harris T.O. et al. (2003) A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen. J Clin Invest 111, 61-70
63Cornacchione P. et al. (1998) Group B streptococci persist inside macrophages. Immunology 93, 86-95
64Teixeira C.F. et al. (2001) Cytochemical study of Streptococcus agalactiae and macrophage interaction. Microsc Res Tech 54, 254-259
65Wilson C.B. and Weaver W.M. (1985) Comparative susceptibility of group B streptococci and Staphylococcus aureus to killing by oxygen metabolites. J Infect Dis 152, 323-329
66Poyart C. et al. (2001) Contribution of Mn-cofactored superoxide dismutase (SodA) to the virulence of Streptococcus agalactiae. Infect Immun 69, 5098-5106
67Spellerberg B. et al. (2000) The cyl genes of Streptococcus agalactiae are involved in the production of pigment. FEMS Microbiol Lett 188, 125-128
68Liu G.Y. et al. (2004) Sword and shield: linked group B streptococcal β-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense. Proc Natl Acad Sci U S A 101, 14491-14496
69Gallo R.L. and Nizet V. (2003) Endogenous production of antimicrobial peptides in innate immunity and human disease. Curr Allergy Asthma Rep 3, 402-409
70Poyart C. et al. (2001) Regulation of D-alanyl-lipoteichoic acid biosynthesis in Streptococcus agalactiae involves a novel two-component regulatory system. J Bacteriol 183, 6324-6334
71Hamilton A. et al. (2006) Penicillin-binding protein 1a promotes resistance of group B streptococcus to antimicrobial peptides. Infect Immun 74, 6179-6187
72Jones A.L. et al. (2007) A streptococcal penicillin-binding protein is critical for resisting innate airway defenses in the neonatal lung. J Immunol 179, 3196-3202
73Maisey H.C. et al. (2008) A group B streptococcal pilus protein promotes phagocyte resistance and systemic virulence. FASEB J 22, 1715-1724
74Ulett G.C. et al. (2005) Mechanisms of group B streptococcal-induced apoptosis of murine macrophages. J Immunol 175, 2555-2562
75Fettucciari K. et al. (2006) Group B Streptococcus induces macrophage apoptosis by calpain activation. J Immunol 176, 7542-7556
76Ulett G.C. et al. (2003) Beta-hemolysin-independent induction of apoptosis of macrophages infected with serotype III group B streptococcus. J Infect Dis 188, 1049-1053
77Carlin A.F. et al. (2007) Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin-like lectins) on human leukocytes. J Bacteriol 189, 1231-1237
78Rojas J. et al. (1983) Pulmonary hemodynamic and ultrastructural changes associated with Group B streptococcal toxemia in adult sheep and newborn lambs. Pediatr Res 17, 1002-1008
79Vallette J.D. Jr. et al. (1995) Effect of an interleukin-1 receptor antagonist on the hemodynamic manifestations of group B streptococcal sepsis. Pediatr Res 38, 704-708
80Mancuso G. et al. (1997) Role of interleukin 12 in experimental neonatal sepsis caused by group B streptococci. Infect Immun 65, 3731-3735
81Vallejo J.G., Baker C.J. and Edwards M.S. (1996) Roles of the bacterial cell wall and capsule in induction of tumor necrosis factor alpha by type III group B streptococci. Infect Immun 64, 5042-5046
82Vallejo J.G., Baker C.J. and Edwards M.S. (1996) Interleukin-6 production by human neonatal monocytes stimulated by type III group B streptococci. J Infect Dis 174, 332-337
83Mancuso G. et al. (2004) Dual role of TLR2 and myeloid differentiation factor 88 in a mouse model of invasive group B streptococcal disease. J Immunol 172, 6324-6329
84Henneke P. et al. (2008) Lipoproteins are critical TLR2 activating toxins in group B streptococcal sepsis. J Immunol 180, 6149-6158
85Henneke P. et al. (2005) Role of lipoteichoic acid in the phagocyte response to group B streptococcus. J Immunol 174, 6449-6455
86Kenzel S. et al. (2006) c-Jun kinase is a critical signaling molecule in a neonatal model of group B streptococcal sepsis. J Immunol 176, 3181-3188
87Raykova V.D. et al. (2003) Nitric oxide-dependent regulation of pro-inflammatory cytokines in group B streptococcal inflammation of rat lung. Ann Clin Lab Sci 33, 62-67
88Ring A. et al. (2002) Synergistic action of nitric oxide release from murine macrophages caused by group B streptococcal cell wall and beta-hemolysin/cytolysin. J Infect Dis 186, 1518-1521
89Maloney C.G. et al. (2000) Induction of cyclooxygenase-2 by human monocytes exposed to group B streptococci. J Leukoc Biol 67, 615-621
90Natarajan G. et al. (2007) Nitric oxide and prostaglandin response to group B streptococcal infection in the lung. Ann Clin Lab Sci 37, 170-176
91Levy O. et al. (2003) Critical role of the complement system in group B streptococcus-induced tumor necrosis factor alpha release. Infect Immun 71, 6344-6353
92Goodrum K.J., McCormick L.L. and Schneider B. (1994) Group B streptococcus-induced nitric oxide production in murine macrophages is CR3 (CD11b/CD18) dependent. Infect Immun 62, 3102-3107
93Henneke P. et al. (2002) Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathways. J Immunol 169, 3970-3977
94Puliti M. et al. (2000) Severity of group B streptococcal arthritis is correlated with β-hemolysin expression. J Infect Dis 182, 824-832
95Ring A. et al. (2002) Group B streptococcal β-hemolysin induces mortality and liver injury in experimental sepsis. J Infect Dis 185, 1745-1753
96Griffiths B.B. and Rhee H. (1992) Effects of haemolysins of groups A and B streptococci on cardiovascular system. Microbios 69, 17-27
97Hensler M.E., Miyamoto S. and Nizet V. (2008) Group B streptococcal β-hemolysin/cytolysin directly impairs cardiomyocyte viability and function PLoS One 3, e2446
98Quirante J., Ceballos R. and Cassady G. (1974) Group B β-hemolytic streptococcal infection in the newborn. I. Early onset infection. Am J Dis Child 128, 659-665
99Berman P.H. and Banker B.Q. (1966) Neonatal meningitis. A clinical and pathological study of 29 cases. Pediatrics 38, 6-24
100Ferrieri P., Burke B. and Nelson J. (1980) Production of bacteremia and meningitis in infant rats with group B streptococcal serotypes. Infect Immun 27, 1023-1032
101Doran K.S. et al. (2005) Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid. J Clin Invest 115, 2499-2507
102Tenenbaum T. et al. (2005) Adherence to and invasion of human brain microvascular endothelial cells are promoted by fibrinogen-binding protein FbsA of Streptococcus agalactiae. Infect Immun 73, 4404-4409
103Doran K.S., Liu G.Y. and Nizet V. (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
104Shin S. et al. (2006) Focal adhesion kinase is involved in type III group B streptococcal invasion of human brain microvascular endothelial cells. Microb Pathog 41, 168-173
105Shin S. and Kim K.S. (2006) RhoA and Rac1 contribute to type III group B streptococcal invasion of human brain microvascular endothelial cells. Biochem Biophys Res Commun 345, 538-542
106Kim Y.S. et al. (1995) Brain injury in experimental neonatal meningitis due to group B streptococci. J Neuropathol Exp Neurol 54, 531-539
107Wahl M. et al. (1988) Mediators of blood-brain barrier dysfunction and formation of vasogenic brain edema. J Cereb Blood Flow Metab 8, 621-634
108Glibetic M. et al. (2001) Group B Streptococci and inducible nitric oxide synthase: modulation by nuclear factor kappa B and ibuprofen. Semin Perinatol 25, 65-69
109McKnight A.A. et al. (1992) Oxygen free radicals and the cerebral arteriolar response to group B streptococci. Pediatr Res 31, 640-644
110Bogdan I. et al. (1997) Tumor necrosis factor-alpha contributes to apoptosis in hippocampal neurons during experimental group B streptococcal meningitis. J Infect Dis 176, 693-697
111Kim K.S., Wass C.A. and Cross A.S. (1997) Blood-brain barrier permeability during the development of experimental bacterial meningitis in the rat. Exp Neurol 145, 253-257
112Lehnardt S. et al. (2006) A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2/MyD88 pathway in microglia. J Immunol 177, 583-592
113Lehnardt S. et al. (2007) TLR2 and caspase-8 are essential for group B Streptococcus-induced apoptosis in microglia. J Immunol 179, 6134-6143
114Ling E.W. et al. (1995) Biochemical mediators of meningeal inflammatory response to group B streptococcus in the newborn piglet model. Pediatr Res 38, 981-987
115Paoletti L.C. and Kasper D.L. (2002) Conjugate vaccines against group B Streptococcus types IV and VII. J Infect Dis 186, 123-126
116Paoletti L.C. and Kasper D.L. (2003) Glycoconjugate vaccines to prevent group B streptococcal infections. Expert Opin Biol Ther 3, 975-984
117Baker C.J. and Edwards M.S. (2003) Group B streptococcal conjugate vaccines. Arch Dis Child 88, 375-378
118Lewis A.L., Nizet V. and Varki A. (2004) Discovery and characterization of sialic acid O-acetylation in group B Streptococcus. Proc Natl Acad Sci U S A 101, 11123-11128
119Santillan D.A., Andracki M.E. and Hunter S.K. (2008) Protective immunization in mice against group B streptococci using encapsulated C5a peptidase. Am J Obstet Gynecol 198, 114e111-116
120Brodeur B.R. et al. (2000) Identification of group B streptococcal Sip protein, which elicits cross-protective immunity. Infect Immun 68, 5610-5618
121Buccato S. et al. (2006) Use of Lactococcus lactis expressing pili from group B Streptococcus as a broad-coverage vaccine against streptococcal disease. J Infect Dis 194, 331-340
122Patten S. et al. (2006) Vaccination for Group B Streptococcus during pregnancy: attitudes and concerns of women and health care providers. Soc Sci Med 63, 347-358
123Chohan L. et al. (2006) Patterns of antibiotic resistance among group B Streptococcus isolates: 2001–2004. Infect Dis Obstet Gynecol 2006, 57492
124Dahesh S. et al. (2008) Point mutation in the group B streptococcal pbp2x gene conferring decreased susceptibility to beta-lactam antibiotics. Antimicrob Agents Chemother 52, 2915-2918
125Kimura K. et al. (2008) First molecular characterization of group B streptococci with reduced penicillin susceptibility. Antimicrob Agents Chemother 52, 2890-2897

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