Review

Department of Pediatric Infectious Diseases, University of Washington & Seattle Children’s Hospital Research Institute, 1900 Ninth Avenue, Seattle, WA 98101–91304, USA.

Email the corresponding author at lakshmi.rajagopal@seattlechildrens.org

Published Online:4 Mar 2009https://doi.org/10.2217/17460913.4.2.201

View article

Abstract

Bacterial infections remain a significant threat to the health of newborns and adults. Group B Streptococci (GBS) are Gram-positive bacteria that are common asymptomatic colonizers of healthy adults. However, this opportunistic organism can also subvert suboptimal host defenses to cause severe invasive disease and tissue damage. The increasing emergence of antibiotic-resistant GBS raises more concerns for sustained measures in treatment of the disease. A number of factors that are important for virulence of GBS have been identified. This review summarizes the functions of some well-characterized virulence factors, with an emphasis on how GBS regulates their expression. Regulatory and signaling molecules are attractive drug targets in the treatment of bacterial infections. Consequently, understanding signaling responses of GBS is essential for elucidation of pathogenesis of GBS infection and for the identification of novel therapeutic agents.

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

1 Berner R: Significance, management and prevention of Streptococcus agalactiae infection during the perinatal period. Expert Rev. Anti. Infect. Ther.2,427–437 (2004).Crossref, Medline, Google Scholar
2 van der Poll T, Opal SM: Host–pathogen interactions in sepsis. Lancet Infect. Dis.8,32–43 (2008).Crossref, Medline, Google Scholar
3 Campbell JR, Hillier SL, Krohn MA, Ferrieri P, Zaleznik DF, Baker CJ: Group B Streptococcal colonization and serotype-specific immunity in pregnant women at delivery. Obstet. Gynecol.96,498–503 (2000).Crossref, Medline, CAS, Google Scholar
4 Mullaney DM: Group B Streptococcal infections in newborns. J. Obstet. Gynecol. Neonatal Nurs.30,649–658 (2001).Crossref, Medline, CAS, Google Scholar
5 Cowgill K, Taylor TH Jr, Schuchat A, Schrag S: Report from the CDC. Awareness of perinatal Group B Streptococcal infection among women of childbearing age in the United States, 1999 and 2002. J. Womens Health (Larchmt)12,527–532 (2003).Crossref, Medline, Google Scholar
6 Lin FY, Weisman LE, Troendle J, Adams K: Prematurity is the major risk factor for late-onset Group B Streptococcus disease. J. Infect. Dis.188,267–271 (2003).Crossref, Medline, Google Scholar
7 Schrag SJ, Zywicki S, Farley MM et al.: Group B Streptococcal disease in the era of intrapartum antibiotic prophylaxis. N. Engl. J. Med.342,15–20 (2000).Crossref, Medline, CAS, Google Scholar
8 Boyer KM, Vogel LC, Gotoff SP, Gadzala CA, Stringer J, Maxted WR: Nosocomial transmission of bacteriophage type 7/11/12 Group B Streptococci in a special care nursery. AMA Am. J. Dis. Child.134,964–966 (1980).CAS, Google Scholar
9 Tumbaga PF, Philip AGS: Perinatal Group B Streptococcal infections: past, present and future. NeoReviews4,65–72 (2003).Crossref, Google Scholar
10 Pettersson K: Perinatal infection with Group B Streptococci. Semin. Fetal Neonatal Med.12,193–197 (2007).Crossref, Medline, Google Scholar
11 Dermer P, Lee C, Eggert J, Few B: A history of neonatal Group B Streptococcus with its related morbidity and mortality rates in the United States. J. Pediatr. Nurs.19,357–363 (2004).Crossref, Medline, Google Scholar
12 American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn: Guidelines for prevention of Group B Streptococcal (GBS) infection by chemoprophylaxis. Pediatrics90,775–778 (1992).Medline, Google Scholar
13 American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn. Revised guidelines for prevention of early-onset Group B Streptococcal (GBS) infection. Pediatrics99,489–496 (1997).Crossref, Medline, Google Scholar
14 Gibbs RS, Schrag S, Schuchat A: Perinatal infections due to Group B Streptococci. Obstet. Gynecol.104,1062–1076 (2004).Crossref, Medline, Google Scholar
15 Lukacs SL, Schoendorf KC, Schuchat A: Trends in sepsis-related neonatal mortality in the United States, 1985–1998. Pediatr. Infect. Dis. J.23,599–603 (2004).Crossref, Medline, Google Scholar
16 Edwards MS, Baker CJ: Group B Streptococcal infections in elderly adults. Clin. Infect. Dis.41,839–847 (2005).Crossref, Medline, Google Scholar
17 Farley MM: Group B Streptococcal disease in nonpregnant adults. Clin. Infect. Dis.33,556–561 (2001).Crossref, Medline, CAS, Google Scholar
18 Andrews JI, Diekema DJ, Hunter SK et al.: Group B Streptococci causing neonatal bloodstream infection: antimicrobial susceptibility and serotyping results from SENTRY centers in the western hemisphere. Am. J. Obstet. Gynecol.183,859–862 (2000).Crossref, Medline, CAS, Google Scholar
19 Bland ML, Vermillion ST, Soper DE, Austin M: Antibiotic resistance patterns of Group B Streptococci in late third-trimester rectovaginal cultures. Am. J. Obstet. Gynecol.184,1125–1126 (2001).Crossref, Medline, CAS, Google Scholar
20 Simoes JA, Aroutcheva AA, Heimler I, Faro S: Antibiotic resistance patterns of Group B Streptococcal clinical isolates. Infect. Dis. Obstet. Gynecol.12,1–8 (2004).Crossref, Medline, CAS, Google Scholar
21 Heelan JS, Hasenbein ME, McAdam AJ: Resistance of Group B Streptococcus to selected antibiotics, including erythromycin and clindamycin. J. Clin. Microbiol.42,1263–1264 (2004).Crossref, Medline, CAS, Google Scholar
22 Dahesh S, Hensler ME, van Sorge NM et al.: Point mutation in the Group B Streptococcal pbp2x gene conferring decreased susceptibility to β-lactam antibiotics. Antimicrob. Agents Chemother.52,2915–2918 (2008).▪ Along with [23] and [24], reports on the mechanisms of spontaneous resistance to penicillin in Group B Streptococci (GBS).Crossref, Medline, CAS, Google Scholar
23 Kimura K, Suzuki S, J Wachino et al.: First molecular characterization of Group B Streptococci with reduced penicillin susceptibility. Antimicrob. Agents Chemother.52,2890–2897 (2008).▪ Along with [22] and [24], reports on the mechanisms of spontaneous resistance to penicillin in GBS.Crossref, Medline, CAS, Google Scholar
24 Nagano N, Nagano Y, Kimura K, Tamai K, Yanagisawa H, Arakawa Y: Genetic heterogeneity in pbp genes among clinically isolated Group B Streptococci with reduced penicillin susceptibility. Antimicrob. Agents Chemother.52(12),4258–4267 (2008).▪ Along with [22] and [23], reports on the mechanisms of spontaneous resistance to penicillin in GBS.Crossref, Medline, CAS, Google Scholar
25 Cieslewicz MJ, Chaffin D, Glusman G et al.: Structural and genetic diversity of Group B Streptococcus capsular polysaccharides. Infect. Immun.73,3096–3103 (2005).Crossref, Medline, CAS, Google Scholar
26 Slotved HC, Kong F, Lambertsen L, Sauer S, Gilbert GL: Serotype IX, a proposed new Streptococcus agalactiae serotype. J. Clin. Microbiol.45,2929–2936 (2007).Crossref, Medline, CAS, Google Scholar
27 Tettelin H, Masignani V, Cieslewicz MJ et al.: Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial ‘pan-genome’. Proc. Natl Acad. Sci. USA102,13950–13955 (2005).Crossref, Medline, CAS, Google Scholar
28 Maisey HC, Doran KS, Nizet V: Recent advances in understanding the molecular basis of Group B Streptococcus virulence. Expert Rev. Mol. Med.10,e27 (2008).▪ Comprehensive review on GBS pathogenesis with an emphasis on its interactions with the host.Crossref, Medline, Google Scholar
29 Miller SI, Mekalanos JJ: Constitutive expression of the phoP regulon attenuates Salmonella virulence and survival within macrophages. J. Bacteriol.172,2485–2490 (1990).Crossref, Medline, CAS, Google Scholar
30 Mouslim C, Delgado M, Groisman EA: Activation of the RcsC/YojN/RcsB phosphorelay system attenuates Salmonella virulence. Mol. Microbiol.54,386–395 (2004).Crossref, Medline, CAS, Google Scholar
31 Stephenson K, Hoch JA: Virulence- and antibiotic resistance-associated two-component signal transduction systems of Gram-positive pathogenic bacteria as targets for antimicrobial therapy. Pharmacol. Ther.93,293–305 (2002).Crossref, Medline, CAS, Google Scholar
32 Johnson CD, Liu LX: Novel antimicrobial targets from combined pathogen and host genetics. Proc. Natl Acad. Sci. USA97,958–959 (2000).Crossref, Medline, CAS, Google Scholar
33 Cohen P: Protein kinases – the major drug targets of the twenty-first century? Nat. Rev. Drug Discov.1,309–315 (2002).Crossref, Medline, CAS, Google Scholar
34 Hoch J, Silhavy TJ: Two-Component Signal Transduction. ASM Press, VA, USA (1995).Google Scholar
35 Glaser P, Rusniok C, Buchrieser C et al.: Genome sequence of Streptococcus agalactiae, a pathogen causing invasive neonatal disease. Mol. Microbiol.45,1499–1513 (2002).Crossref, Medline, CAS, Google Scholar
36 Tettelin H, Masignani V, Cieslewicz MJ et al.: Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae. Proc. Natl Acad. Sci. USA99,12391–12396 (2002).Crossref, Medline, CAS, Google Scholar
37 Lamy MC, Zouine M, Fert J et al.: CovS/CovR of Group B Streptococcus: a two-component global regulatory system involved in virulence. Mol. Microbiol.54,1250–1268 (2004).▪▪ One of two independent studies on the CovR/S system in GBS.Crossref, Medline, CAS, Google Scholar
38 Jiang SM, Cieslewicz MJ, Kasper DL, Wessels MR: Regulation of virulence by a two-component system in Group B Streptococcus. J. Bacteriol.187,1105–1113 (2005).▪▪ One of two independent studies on the CovR/S system in GBS.Crossref, Medline, CAS, Google Scholar
39 Jiang SM, Ishmael N, Hotopp JD et al.: Variation in the Group B Streptococcus CsrRS regulon and effects on pathogenicity. J. Bacteriol.190,1956–1965 (2008).Crossref, Medline, CAS, Google Scholar
40 Poyart C, Lamy MC, Boumaila C, Fiedler F, Trieu-Cuot P: Regulation of D-alanyl-lipotechoic acid biosynthesis in Streptococcus agalactiae involves a novel two-component regulatory system. J. Bacteriol.183,6324–6334 (2001).Crossref, Medline, CAS, Google Scholar
41 Poyart C, Pellegrini E, Marceau M et al.: Attenuated virulence of Streptococcus agalactiae deficient in D-alanyl-lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells. Mol. Microbiol.49,1615–1625 (2003).▪▪ Interesting article on regulation of GBS resistance to antimicrobial peptides by the two-component systems DltR/S.Crossref, Medline, CAS, Google Scholar
42 Spellerberg B, Rozdzinski E, Martin S, Weber-Heynemann J, Lutticken R: rgf encodes a novel two-component signal transduction system of Streptococcus agalactiae. Infect. Immun.70,2434–2440 (2002).▪ Describes regulation of C5a peptidase by RgfB/C.Google Scholar
43 Quach D, van Sorge NM, Kristian SA, Bryan JD, Shelver DW, Doran KS: The CiaR response regulator in Group B Streptococcus promotes intracellular survival and resistance to innate immune defenses. J. Bacteriol. (2008) (Epub ahead of print).▪ Describes the role of CiaR/H in GBS virulence.Medline, Google Scholar
44 Ulrich LE, Koonin EV, Zhulin IB: One-component systems dominate signal transduction in prokaryotes. Trends Microbiol.13,52–56 (2005).Crossref, Medline, CAS, Google Scholar
45 Kreikemeyer B, McIver KS, Podbielski A: Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen–host interactions. Trends Microbiol.11,224–232 (2003).Crossref, Medline, CAS, Google Scholar
46 Shelver D, Rajagopal L, Harris TO, Rubens CE: MtaR, a regulator of methionine transport, is critical for survival of Group B Streptococcus in vivo. J. Bacteriol.185,6592–6599 (2003).Crossref, Medline, CAS, Google Scholar
47 Bryan JD, Liles R, Cvek U, Trutschl M, Shelver D: Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor. BMC Genomics9,607 (2008).▪ Reports genes regulated by MtaR.Crossref, Medline, Google Scholar
48 Gutekunst H, Eikmanns BJ, Reinscheid DJ: Analysis of RogB-controlled virulence mechanisms and gene repression in Streptococcus agalactiae. Infect. Immun.71,5056–5064 (2003).▪ Describes regulation of CpsA and FbsA by RogB.Crossref, Medline, CAS, Google Scholar
49 Samen UM, Eikmanns BJ, Reinscheid DJ: The transcriptional regulator RovS controls the attachment of Streptococcus agalactiae to human epithelial cells and the expression of virulence genes. Infect. Immun.74,5625–5635 (2006).▪ Describes regulation of CylE, SodA and FbsA by RovS.Crossref, Medline, CAS, Google Scholar
50 Rajagopal L, Clancy A, Rubens CE: A eukaryotic type serine/threonine kinase and phosphatase in Streptococcus agalactiae reversibly phosphorylate an inorganic pyrophosphatase and affect growth, cell segregation, and virulence. J. Biol. Chem.278,14429–14441 (2003).Crossref, Medline, CAS, Google Scholar
51 Rajagopal L, Vo A, Silvestroni A, Rubens CE: Regulation of purine biosynthesis by a eukaryotic-type kinase in Streptococcus agalactiae. Mol. Microbiol.56,1329–1346 (2005).Crossref, Medline, CAS, Google Scholar
52 Rajagopal L, Vo A, Silvestroni A, Rubens CE: Regulation of cytotoxin expression by converging eukaryotic-type and two-component signaling mechanisms in Streptococcus agalactiae. Mol. Microbiol.62,941–957 (2006).Crossref, Medline, CAS, Google Scholar
53 Lin WJ, Walthers D, Connelly JE et al.: Threonine phosphorylation prevents promoter DNA binding of the Group B Streptococcus response regulator CovR. Mol. Microbiol. (2009) (Epub ahead of print).▪▪ Elucidates the link between two component (CovR) and serine/threonine kinase (Stk1) signaling systems in GBS.Google Scholar
54 Churchward G: The two faces of Janus: virulence gene regulation by CovR/S in Group A Streptococci. Mol. Microbiol.64,34–41 (2007).Crossref, Medline, CAS, Google Scholar
55 Hondorp ER, McIver KS: The Mga virulence regulon: infection where the grass is greener. Mol. Microbiol.66,1056–1065 (2007).Crossref, Medline, CAS, Google Scholar
56 Novick RP: Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol.48,1429–1449 (2003).Crossref, Medline, CAS, Google Scholar
57 Novick RP: Medicine. Combating impervious bugs. Science319,910–911 (2008).Crossref, Medline, CAS, Google Scholar
58 Aroian R, van der Goot FG: Pore-forming toxins and cellular non-immune defenses (CNIDs). Curr. Opin. Microbiol.10,57–61 (2007).Crossref, Medline, CAS, Google Scholar
59 Gonzalez MR, Bischofberger M, Pernot L, van der Goot FG, Freche B: Bacterial pore-forming toxins: the (w)hole story? Cell. Mol. Life Sci.65,493–507 (2008).Crossref, Medline, CAS, Google Scholar
60 Nizet V, Gibson RL, Chi EY, Framson PE, Hulse M, Rubens CE: Group B Streptococcal β-hemolysin expression is associated with injury of lung epithelial cells. Infect. Immun.64,3818–3826 (1996).Crossref, Medline, CAS, Google Scholar
61 Nizet V, Gibson RL, Rubens CE: The role of Group B Streptococci β-hemolysin expression in newborn lung injury. Adv. Exp. Med. Biol.418,627–630 (1997).Crossref, Medline, CAS, Google Scholar
62 Gibson RL, Nizet V, Rubens CE: Group B Streptococcal β-hemolysin promotes injury of lung microvascular endothelial cells. Pediatr. Res.45,626–634 (1999).Crossref, Medline, CAS, Google Scholar
63 Doran KS, Chang JC, Benoit VM, Eckmann L, Nizet V: 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 (2002).Crossref, Medline, CAS, Google Scholar
64 Doran KS, Liu GY, Nizet V: 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 (2003).Crossref, Medline, CAS, Google Scholar
65 Hensler ME, Miyamoto S, Nizet V: Group B Streptococcal β-hemolysin/cytolysin directly impairs cardiomyocyte viability and function. PLoS ONE3,e2446 (2008).Crossref, Medline, Google Scholar
66 Ring A, Braun JS, Pohl J, Nizet V, Stremmel W, Shenep JL: Group B Streptococcal β-hemolysin induces mortality and liver injury in experimental sepsis. J. Infect. Dis.185,1745–1753 (2002).Crossref, Medline, CAS, Google Scholar
67 Ring A, Braun JS, Nizet V, Stremmel W, Shenep JL: Group B Streptococcal β-hemolysin induces nitric oxide production in murine macrophages. J. Infect. Dis.182,150–157 (2000).Crossref, Medline, CAS, Google Scholar
68 Hensler ME, Liu GY, Sobczak S, Benirschke K, Nizet V, Heldt GP: 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 (2005).Crossref, Medline, Google Scholar
69 Puliti M, Nizet V, von Hunolstein C et al.: Severity of Group B Streptococcal arthritis is correlated with β-hemolysin expression. J. Infect. Dis.182,824–832 (2000).Crossref, Medline, CAS, Google Scholar
70 Pritzlaff CA, Chang JC, Kuo SP, Tamura GS, Rubens CE, Nizet V: Genetic basis for the β-haemolytic/cytolytic activity of Group B Streptococcus. Mol. Microbiol.39,236–247 (2001).Crossref, Medline, CAS, Google Scholar
71 Spellerberg B, Pohl B, Haase G, Martin S, Weber-Heynemann J, Lutticken R: Identification of genetic determinants for the hemolytic activity of Streptococcus agalactiae by ISS1 transposition. J. Bacteriol.181,3212–3219 (1999).Crossref, Medline, CAS, Google Scholar
72 Forquin MP, Tazi A, Rosa-Fraile M, Poyart C, Trieu-Cuot P, Dramsi S: The putative glycosyltransferase-encoding gene cylJ and the Group B Streptococcus (GBS)-specific gene cylK modulate hemolysin production and virulence of GBS. Infect. Immun.75,2063–2066 (2007).Crossref, Medline, CAS, Google Scholar
73 Gottschalk B, Broker G, Kuhn M, Aymanns S, Gleich-Theurer U, Spellerberg B: Transport of multidrug resistance substrates by the Streptococcus agalactiae hemolysin transporter. J. Bacteriol.188,5984–5992 (2006).Crossref, Medline, CAS, Google Scholar
74 Nizet V: Streptococcal β-hemolysins: genetics and role in disease pathogenesis. Trends Microbiol.10,575–580 (2002).Crossref, Medline, CAS, Google Scholar
75 Spellerberg B, Martin S, Brandt C, Lutticken R: The cyl genes of Streptococcus agalactiae are involved in the production of pigment. FEMS Microbiol. Lett.188,125–128 (2000).Crossref, Medline, CAS, Google Scholar
76 Tapsall JW: Pigment production by Lancefield-Group-B Streptococci (Streptococcus agalactiae). J. Med. Microbiol.21,75–81 (1986).Crossref, Medline, CAS, Google Scholar
77 Liu GY, Doran KS, Lawrence T et al.: Sword and shield: linked Group B Streptococcal β-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense. Proc. Natl Acad. Sci. USA101,14491–14496 (2004).Crossref, Medline, CAS, Google Scholar
78 Fang FC: Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat. Rev. Microbiol.2,820–832 (2004).Crossref, Medline, CAS, Google Scholar
79 Rosa-Fraile M, Rodriguez-Granger J, Haidour-Benamin A, Cuerva JM, Sampedro A: Granadaene: proposed structure of the Group B Streptococcus polyenic pigment. Appl. Environ. Microbiol.72,6367–6370 (2006).Crossref, Medline, CAS, Google Scholar
80 Krinsky NI, Yeum KJ: Carotenoid-radical interactions. Biochem. Biophys. Res. Commun.305,754–760 (2003).Crossref, Medline, CAS, Google Scholar
81 Mathews MM, Sistrom WR: Function of carotenoid pigments in non-photosynthetic bacteria. Nature184(Suppl. 24),1892–1893 (1959).Crossref, Medline, CAS, Google Scholar
82 Rajagopal L, Sundari CS, Balasubramanian D, Sonti RV: The bacterial pigment xanthomonadin offers protection against photodamage. FEBS Lett.415,125–128 (1997).Crossref, Medline, CAS, Google Scholar
83 Ulijasz AT, Falk SP, Weisblum B: Phosphorylation of the RitR DNA-binding domain by a Ser–Thr phosphokinase: implications for global gene regulation in the streptococci. Mol. Microbiol.71(2),382–390. (2008).▪ Recent evidence for the link between response regulators and ser/thr kinases in other streptococci.Crossref, Medline, Google Scholar
84 Lang S, Palmer M: Characterization of Streptococcus agalactiae CAMP factor as a pore-forming toxin. J. Biol. Chem.278,38167–38173 (2003).Crossref, Medline, CAS, Google Scholar
85 Podbielski A, Blankenstein O, Lutticken R: Molecular characterization of the cfb gene encoding Group B Streptococcal CAMP-factor. Med. Microbiol. Immunol. (Berl.)183,239–256 (1994).Crossref, Medline, CAS, Google Scholar
86 Jurgens D, Sterzik B, Fehrenbach FJ: Unspecific binding of Group B Streptococcal cocytolysin (CAMP factor) to immunoglobulins and its possible role in pathogenicity. J. Exp. Med.165,720–732 (1987).Crossref, Medline, CAS, Google Scholar
87 Skalka B, Smola J: Lethal effect of CAMP-factor and UBERIS-factor – a new finding about diffusible exosubstances of Streptococcus agalactiae and Streptococcus uberis. Zentralbl. Bakteriol. A249,190–194 (1981).Medline, CAS, Google Scholar
88 Lang S, Palmer M: Characterization of Streptococcus agalactiae CAMP factor as a pore-forming toxin. J. Biol. Chem.278,38167–38173 (2003).Crossref, Medline, CAS, Google Scholar
89 Lang S, Xue J, Guo Z, Palmer M: Streptococcus agalactiae CAMP factor binds to GPI-anchored proteins. Med. Microbiol. Immunol.196,1–10 (2007).Crossref, Medline, CAS, Google Scholar
90 Hensler ME, Quach D, Hsieh CJ, Doran KS, Nizet V: CAMP factor is not essential for systemic virulence of Group B Streptococcus. Microb. Pathog.44,84–88 (2008).▪ Examined virulence properties of a Christie Atkins Munch Peterson factor deficient GBS strain.Crossref, Medline, CAS, Google Scholar
91 Jiang SM, Ishmael N, Hotopp JD et al.: Variation in the Group B Streptococcus CsrRS regulon and effects on pathogenicity. J. Bacteriol.190,1956–1965 (2008).Crossref, Medline, CAS, Google Scholar
92 Marques MB, Kasper DL, Pangburn MK, Wessels MR: Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III Group B Streptococci. Infect. Immun.60,3986–3993 (1992).Crossref, Medline, CAS, Google Scholar
93 Campbell JR, Baker CJ, Edwards MS: Deposition and degradation of C3 on type III Group B Streptococci. Infect. Immun.59,1978–1983 (1991).Crossref, Medline, CAS, Google Scholar
94 Baker CJ, Kasper DL: Correlation of maternal antibody deficiency with susceptibility to neonatal Group B Streptococcal infection. N. Engl. J. Med.294,753–756 (1976).Crossref, Medline, CAS, Google Scholar
95 Rubens CE, Wessels MR, Heggen LM, Kasper DL: Transposon mutagenesis of type III Group B Streptococcus: correlation of capsule expression with virulence. Proc. Natl Acad. Sci. USA84,7208–7212 (1987).Crossref, Medline, CAS, Google Scholar
96 Wessels MR, Rubens CE, Benedi VJ, Kasper DL: Definition of a bacterial virulence factor: sialylation of the Group B Streptococcal capsule. Proc. Natl Acad. Sci. USA86,8983–8987 (1989).Crossref, Medline, CAS, Google Scholar
97 Martin TR, Ruzinski JT, Rubens CE, Chi EY, Wilson CB: The effect of type-specific polysaccharide capsule on the clearance of Group B Streptococci from the lungs of infant and adult rats. J. Infect. Dis.165,306–314 (1992).Crossref, Medline, CAS, Google Scholar
98 Wessels MR, Haft RF, Heggen LM, Rubens CE: Identification of a genetic locus essential for capsule sialylation in type III Group B Streptococci. Infect. Immun.60,392–400 (1992).Crossref, Medline, CAS, Google Scholar
99 Marques MB, Kasper DL, Shroff A, Michon F, Jennings HJ, Wessels MR: Functional activity of antibodies to the group B polysaccharide of Group B Streptococci elicited by a polysaccharide-protein conjugate vaccine. Infect. Immun.62,1593–1599 (1994).Crossref, Medline, CAS, Google Scholar
100 Paoletti LC, Kasper DL: Glycoconjugate vaccines to prevent Group B Streptococcal infections. Expert Opin. Biol. Ther.3,975–984 (2003).Crossref, Medline, CAS, Google Scholar
101 Paoletti LC, Kasper DL, Michon F et al.: An oligosaccharide-tetanus toxoid conjugate vaccine against type III Group B Streptococcus. J. Biol. Chem.265,18278–18283 (1990).Crossref, Medline, CAS, Google Scholar
102 Paoletti LC, Kasper DL: Conjugate vaccines against Group B Streptococcus types IV and VII. J. Infect. Dis.186,123–126 (2002).Crossref, Medline, Google Scholar
103 Johri AK, Paoletti LC, Glaser P et al.: Group B Streptococcus: global incidence and vaccine development. Nat. Rev. Microbiol.4,932–942 (2006).Crossref, Medline, CAS, Google Scholar
104 Edwards MS: Group B Streptococcal conjugate vaccine: a timely concept for which the time has come. Hum. Vaccin.4,444–448 (2008).Crossref, Medline, Google Scholar
105 Paoletti LC, Guttormsen HK, Christian MS, Hoberman AM, McInnes P: Neither antibody to a Group B Streptococcal conjugate vaccine nor the vaccine itself is teratogenic in rabbits. Hum. Vaccin.4,435–443 (2008).Crossref, Medline, CAS, Google Scholar
106 Lewis AL, Nizet V, Varki A: Discovery and characterization of sialic acid O-acetylation in Group B Streptococcus. Proc. Natl Acad. Sci. USA101,11123–11128 (2004).▪▪ First report that describes O-acetylation of the GBS capsular polysaccharide.Crossref, Medline, CAS, Google Scholar
107 Berry DS, Lynn F, Lee CH, Frasch CE, Bash MC: Effect of O-acetylation of Neisseria meningitidis serogroup A capsular polysaccharide on development of functional immune responses. Infect. Immun.70,3707–3713 (2002).Crossref, Medline, CAS, Google Scholar
108 McNeely TB, Staub JM, Rusk CM, Blum MJ, Donnelly JJ: Antibody responses to capsular polysaccharide backbone and O-acetate side groups of Streptococcus pneumoniae type 9V in humans and rhesus macaques. Infect. Immun.66,3705–3710 (1998).Crossref, Medline, CAS, Google Scholar
109 Lewis AL, Cao H, Patel SK et al.: NeuA sialic acid O-acetylesterase activity modulates O-acetylation of capsular polysaccharide in Group B Streptococcus. J. Biol. Chem.282,27562–27571 (2007).Crossref, Medline, CAS, Google Scholar
110 Hulse ML, Smith S, Chi EY, Pham A, Rubens CE: Effect of type III Group B Streptococcal capsular polysaccharide on invasion of respiratory epithelial cells. Infect. Immun.61,4835–4841 (1993).Crossref, Medline, CAS, Google Scholar
111 Tamura GS, Kuypers JM, Smith S, Raff H, Rubens CE: Adherence of Group B Streptococci to cultured epithelial cells: roles of environmental factors and bacterial surface components. Infect. Immun.62,2450–2458 (1994).Crossref, Medline, CAS, Google Scholar
112 Nizet V, Kim KS, Stins M et al.: Invasion of brain microvascular endothelial cells by Group B Streptococci. Infect. Immun.65,5074–5081 (1997).Crossref, Medline, CAS, Google Scholar
113 Paoletti LC, Ross RA, Johnson KD: Cell growth rate regulates expression of Group B Streptococcus type III capsular polysaccharide. Infect. Immun.64,1220–1226 (1996).Crossref, Medline, CAS, Google Scholar
114 Ross RA, Madoff LC, Paoletti LC: Regulation of cell component production by growth rate in the Group B Streptococcus. J. Bacteriol.181,5389–5394 (1999).Crossref, Medline, CAS, Google Scholar
115 Johri AK, Patwardhan V, Paoletti LC: Growth rate and oxygen regulate the interactions of Group B Streptococcus with polarized respiratory epithelial cells. Can. J. Microbiol.51,283–286 (2005).Crossref, Medline, CAS, Google Scholar
116 Malin G, Paoletti LC: Use of a dynamic in vitro attachment and invasion system (DIVAS) to determine influence of growth rate on invasion of respiratory epithelial cells by Group B Streptococcus. Proc. Natl Acad. Sci. USA98,13335–13340 (2001).Crossref, Medline, CAS, Google Scholar
117 Poyart C, Pellegrini E, Gaillot O, Boumaila C, Baptista M, Trieu-Cuot P: Contribution of Mn-cofactored superoxide dismutase (SodA) to the virulence of Streptococcus agalactiae. Infect. Immun.69,5098–5106 (2001).Crossref, Medline, CAS, Google Scholar
118 Takahashi S, Nagano Y, Nagano N, Hayashi O, Taguchi F, Okuwaki Y: Role of C5a-ase in Group B Streptococcal resistance to opsonophagocytic killing. Infect. Immun.63,4764–4769 (1995).Crossref, Medline, CAS, Google Scholar
119 Bohnsack JF, Widjaja K, Ghazizadeh S et al.: A role for C5 and C5a-ase in the acute neutrophil response to Group B Streptococcal infections. J. Infect. Dis.175,847–855 (1997).Crossref, Medline, CAS, Google Scholar
120 Cheng Q, Stafslien D, Purushothaman SS, Cleary P: The Group B Streptococcal C5a peptidase is both a specific protease and an invasin. Infect. Immun.70,2408–2413 (2002).Crossref, Medline, CAS, Google Scholar
121 Beckmann C, Waggoner JD, Harris TO, Tamura GS, Rubens CE: 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 (2002).Crossref, Medline, CAS, Google Scholar
122 Tamura GS, Hull JR, Oberg MD, Castner DG: 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 (2006).Crossref, Medline, CAS, Google Scholar
123 Hull JR, Tamura GS, Castner DG: Interactions of the streptococcal C5a peptidase with human fibronectin. Acta Biomater.4,504–513 (2008).Crossref, Medline, CAS, Google Scholar
124 Cheng Q, Debol S, Lam H et al.: Immunization with C5a peptidase or peptidase-type III polysaccharide conjugate vaccines enhances clearance of Group B Streptococci from lungs of infected mice. Infect. Immun.70,6409–6415 (2002).Crossref, Medline, CAS, Google Scholar
125 Santillan DA, Andracki ME, Hunter SK: Protective immunization in mice against Group B Streptococci using encapsulated C5a peptidase. Am. J. Obstet. Gynecol.198,114 e1–e6 (2008).Crossref, Medline, Google Scholar
126 Harris TO, Shelver DW, Bohnsack JF, Rubens CE: A novel streptococcal surface protease promotes virulence, resistance to opsonophagocytosis, and cleavage of human fibrinogen. J. Clin. Invest.111,61–70 (2003).Crossref, Medline, CAS, Google Scholar
127 Bryan JD, Shelver DW: Streptococcus agalactiae CspA is a serine protease that inactivates chemokines. J. Bacteriol. (2008) (Epub ahead of print).Google Scholar
128 Dramsi S, Caliot E, Bonne I et al.: Assembly and role of pili in Group B Streptococci. Mol. Microbiol.60,1401–1413 (2006).Crossref, Medline, CAS, Google Scholar
129 Nobbs AH, Rosini R, Rinaudo CD, Maione D, Grandi G, Telford JL: Sortase A utilizes an ancillary protein anchor for efficient cell wall anchoring of pili in Streptococcus agalactiae. Infect. Immun.76,3550–3560 (2008).Crossref, Medline, CAS, Google Scholar
130 Lalioui L, Pellegrini E, Dramsi S et al.: The SrtA sortase of Streptococcus agalactiae is required for cell wall anchoring of proteins containing the LPXTG motif, for adhesion to epithelial cells, and for colonization of the mouse intestine. Infect. Immun.73,3342–3350 (2005).Crossref, Medline, CAS, Google Scholar
131 Hancock RE, Diamond G: The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol.8,402–410 (2000).Crossref, Medline, CAS, Google Scholar
132 Nizet V, Gallo RL: Surviving innate immunity. Trends Microbiol.10,358–359 (2002).Crossref, Medline, CAS, Google Scholar
133 Peschel A: How do bacteria resist human antimicrobial peptides? Trends Microbiol.10,179–186 (2002).Crossref, Medline, CAS, Google Scholar
134 Gryllos I, Tran-Winkler HJ, Cheng MF et al.: Induction of Group A Streptococcus virulence by a human antimicrobial peptide. Proc. Natl Acad. Sci. USA105,16755–16760 (2008).Crossref, Medline, CAS, Google Scholar
135 Froehlich BJ, Bates C, Scott JR: Streptococcus pyogenes CovR/S mediates growth in iron starvation and in the presence of the human cationic antimicrobial peptide LL-37. J. Bacteriol.191(2),673–677 (2009).Crossref, Medline, CAS, Google Scholar
136 Spratt BG, Cromie KD: Penicillin-binding proteins of gram-negative bacteria. Rev. Infect. Dis.10,699–711 (1988).Crossref, Medline, CAS, Google Scholar
137 Georgopapadakou NH, Liu FY: Penicillin-binding proteins in bacteria. Antimicrob. Agents Chemother.18,148–157 (1980).Crossref, Medline, CAS, Google Scholar
138 Zapun A, Contreras-Martel C, Vernet T: Penicillin-binding proteins and β-lactam resistance. FEMS Microbiol. Rev.32,361–385 (2008).Crossref, Medline, CAS, Google Scholar
139 Jones AL, Needham RH, Clancy A, Knoll KM, Rubens CE: Penicillin-binding proteins in Streptococcus agalactiae: a novel mechanism for evasion of immune clearance. Mol. Microbiol.47,247–256 (2003).Crossref, Medline, CAS, Google Scholar
140 Jones AL, Knoll KM, Rubens CE: Identification of Streptococcus agalactiae virulence genes in the neonatal rat sepsis model using signature-tagged mutagenesis. Mol. Microbiol.37,1444–1455 (2000).Crossref, Medline, CAS, Google Scholar
141 Jones AL, Mertz RH, Carl DJ, Rubens CE: A streptococcal penicillin-binding protein is critical for resisting innate airway defenses in the neonatal lung. J. Immunol.179,3196–3202 (2007).Crossref, Medline, CAS, Google Scholar
142 Hamilton A, Popham DL, Carl DJ, Lauth X, Nizet V, Jones AL: Penicillin-binding protein 1a promotes resistance of Group B Streptococcus to antimicrobial peptides. Infect. Immun.74,6179–6187 (2006).Crossref, Medline, CAS, Google Scholar
143 Lauer P, Rinaudo CD, Soriani M et al.: Genome analysis reveals pili in Group B Streptococcus. Science309,105 (2005).Crossref, Medline, CAS, Google Scholar
144 Pezzicoli A, Santi I, Lauer P et al.: Pilus backbone contributes to Group B Streptococcus paracellular translocation through epithelial cells. J. Infect. Dis.198,890–898 (2008).Crossref, Medline, Google Scholar
145 Maisey HC, Hensler M, Nizet V, Doran KS: Group B Streptococcal pilus proteins contribute to adherence to and invasion of brain microvascular endothelial cells. J. Bacteriol.189,1464–1467 (2007).Crossref, Medline, CAS, Google Scholar
146 Maisey HC, Quach D, Hensler ME et al.: A Group B Streptococcal pilus protein promotes phagocyte resistance and systemic virulence. FASEB J.22,1715–1724 (2008).Crossref, Medline, CAS, Google Scholar
147 Rosini R, Rinaudo CD, Soriani M et al.: Identification of novel genomic islands coding for antigenic pilus-like structures in Streptococcus agalactiae. Mol. Microbiol.61,126–141 (2006).Crossref, Medline, CAS, Google Scholar
148 Buccato S, Maione D, Rinaudo CD et al.: Use of Lactococcus lactis expressing pili from Group B Streptococcus as a broad-coverage vaccine against streptococcal disease. J. Infect. Dis.194,331–340 (2006).Crossref, Medline, CAS, Google Scholar
149 Telford JL, Barocchi MA, Margarit I, Rappuoli R, Grandi G: Pili in Gram-positive pathogens. Nat. Rev. Microbiol.4,509–519 (2006).Crossref, Medline, CAS, Google Scholar
150 Maione D, Margarit I, Rinaudo CD et al.: Identification of a universal Group B Streptococcus vaccine by multiple genome screen. Science309,148–150 (2005).▪ Explores cell surface proteins as a universal vaccine for GBS.Crossref, Medline, CAS, Google Scholar
151 Schubert A, Zakikhany K, Schreiner M et al.: A fibrinogen receptor from Group B Streptococcus interacts with fibrinogen by repetitive units with novel ligand binding sites. Mol. Microbiol.46,557–569 (2002).Crossref, Medline, CAS, Google Scholar
152 Jacobsson K: A novel family of fibrinogen-binding proteins in Streptococcus agalactiae. Vet. Microbiol.96,103–113 (2003).Crossref, Medline, CAS, Google Scholar
153 Gutekunst H, Eikmanns BJ, Reinscheid DJ: The novel fibrinogen-binding protein FbsB promotes Streptococcus agalactiae invasion into epithelial cells. Infect. Immun.72,3495–3504 (2004).Crossref, Medline, CAS, Google Scholar
154 Spellerberg B, Rozdzinski E, Martin S et al.: Lmb, a protein with similarities to the LraI adhesin family, mediates attachment of Streptococcus agalactiae to human laminin. Infect. Immun.67,871–878 (1999).Crossref, Medline, CAS, Google Scholar
155 Tenenbaum T, Spellerberg B, Adam R, Vogel M, Kim KS, Schroten H: Streptococcus agalactiae invasion of human brain microvascular endothelial cells is promoted by the laminin-binding protein Lmb. Microbes Infect.9,714–720 (2007).Crossref, Medline, CAS, Google Scholar
156 Siboo IR, Chambers HF, Sullam PM: Role of SraP, a serine-rich surface protein of Staphylococcus aureus, in binding to human platelets. Infect. Immun.73,2273–2280 (2005).Crossref, Medline, CAS, Google Scholar
157 Takamatsu D, Bensing BA, Cheng H et al.: Binding of the Streptococcus gordonii surface glycoproteins GspB and Hsa to specific carbohydrate structures on platelet membrane glycoprotein Ibα. Mol. Microbiol.58,380–392 (2005).Crossref, Medline, CAS, Google Scholar
158 Seifert KN, Adderson EE, Whiting AA, Bohnsack JF, Crowley PJ, Brady LJ: A unique serine-rich repeat protein (Srr-2) and novel surface antigen (ε) associated with a virulent lineage of serotype III Streptococcus agalactiae. Microbiology152,1029–1040 (2006).Crossref, Medline, CAS, Google Scholar
159 Samen U, Eikmanns BJ, Reinscheid DJ, Borges F: 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 (2007).Crossref, Medline, CAS, Google Scholar
160 Santi I, Scarselli M, Mariani M et al.: BibA: a novel immunogenic bacterial adhesin contributing to Group B Streptococcus survival in human blood. Mol. Microbiol.63,754–767 (2007).Crossref, Medline, CAS, Google Scholar
161 Mereghetti L, Sitkiewicz I, Green NM, Musser JM: Remodeling of the Streptococcus agalactiae transcriptome in response to growth temperature. PLoS ONE3,e2785 (2008).▪▪ Adaptation of GBS to conditions that mimic fever.Crossref, Medline, Google Scholar
162 Michel JL, Madoff LC, Kling DE, Kasper DL, Ausubel FM: Cloned α and β C-protein antigens of Group B Streptococci elicit protective immunity. Infect. Immun.59,2023–2028 (1991).Crossref, Medline, CAS, Google Scholar
163 Johnson DR, Ferrieri P: Group B Streptococcal Ibc protein antigen: distribution of two determinants in wild-type strains of common serotypes. J. Clin. Microbiol.19,506–510 (1984).Crossref, Medline, CAS, Google Scholar
164 Baron MJ, Bolduc GR, Goldberg MB, Auperin TC, Madoff LC: αC protein of Group B Streptococcus binds host cell surface glycosaminoglycan and enters cells by an actin-dependent mechanism. J. Biol. Chem.279,24714–24723 (2004).Crossref, Medline, CAS, Google Scholar
165 Baron MJ, Filman DJ, Prophete GA, Hogle JM, Madoff LC: Identification of a glycosaminoglycan binding region of the αC protein that mediates entry of Group B Streptococci into host cells. J. Biol. Chem.282,10526–10536 (2007).Crossref, Medline, CAS, Google Scholar
166 Bolduc GR, Madoff LC: The Group B Streptococcal α C protein binds α1β 1-integrin through a novel KTD motif that promotes internalization of GBS within human epithelial cells. Microbiology153,4039–4049 (2007).Crossref, Medline, CAS, Google Scholar
167 Doran KS, Engelson EJ, Khosravi A et al.: Blood–brain barrier invasion by Group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid. J. Clin. Invest.115,2499–2507 (2005).Crossref, Medline, CAS, Google Scholar
168 Lin B, Hollingshead SK, Coligan JE, Egan ML, Baker JR, Pritchard DG: Cloning and expression of the gene for Group B Streptococcal hyaluronate lyase. J. Biol. Chem.269,30113–30116 (1994).Crossref, Medline, CAS, Google Scholar
169 Gase K, Ozegowski J, Malke H: The Streptococcus agalactiaehylB gene encoding hyaluronate lyase: completion of the sequence and expression analysis. Biochimica Biophysica Acta1398,86–98 (1998).Crossref, Medline, CAS, Google Scholar
170 Laurent TC, Fraser JR: Hyaluronan. FASEB J.6,2397–2404 (1992).Crossref, Medline, CAS, Google Scholar
171 Lindahl U, Hook M: Glycosaminoglycans and their binding to biological macromolecules. Annu. Rev. Biochem.47,385–417 (1978).Crossref, Medline, CAS, Google Scholar
172 Li S, Jedrzejas MJ: Hyaluronan binding and degradation by Streptococcus agalactiae hyaluronate lyase. J. Biol. Chem.276,41407–41416 (2001).Crossref, Medline, CAS, Google Scholar
173 Pritchard DG, Lin B, Willingham TR, Baker JR: Characterization of the Group B Streptococcal hyaluronate lyase. Arch. Biochem. Biophys.315,431–437 (1994).Crossref, Medline, CAS, Google Scholar
174 Akhtar MS, Krishnan MY, Bhakuni V: Insights into the mechanism of action of hyaluronate lyase: role of C-terminal domain and Ca²⁺ in the functional regulation of enzyme. J. Biol. Chem.281,28336–28344 (2006).Crossref, Medline, CAS, Google Scholar
175 Milligan TW, Baker CJ, Straus DC, Mattingly SJ: Association of elevated levels of extracellular neuraminidase with clinical isolates of type III Group B Streptococci. Infect. Immun.21,738–746 (1978).Crossref, Medline, CAS, Google Scholar
176 Juul SE, Kinsella MG, Truog WE, Gibson RL, Redding GJ: Lung hyaluronan decreases during Group B Streptococcal pneumonia in neonatal piglets. American Am. J. Respir. Crit. Care Med.153,1567–1570 (1996).Crossref, Medline, CAS, Google Scholar
177 Johri AK, Margarit I, Broenstrup M et al.: Transcriptional and proteomic profiles of Group B Streptococcus type V reveal potential adherence proteins associated with high-level invasion. Infect. Immun.75,1473–1483 (2007).▪ Describes changes in GBS gene and protein expression under conditions that mimic invasion.Crossref, Medline, CAS, Google Scholar
178 Clancy A, Loar JW, Speziali CD, Oberg M, Heinrichs DE, Rubens CE: Evidence for siderophore-dependent iron acquisition in Group B Streptococcus. Mol. Microbiol.59,707–721 (2006).Crossref, Medline, CAS, Google Scholar
179 Mereghetti L, Sitkiewicz I, Green NM, Musser JM: Extensive adaptive changes occur in the transcriptome of Streptococcus agalactiae (Group B Streptococcus) in response to incubation with human blood. PLoS ONE3,e3143 (2008).▪▪ Adaptation of GBS to human blood.Crossref, Medline, Google Scholar
180 Gryllos I, Grifantini R, Colaprico A et al.: Mg²⁺ signalling defines the Group A Streptococcal CsrRS (CovRS) regulon. Mol. Microbiol.65,671–683 (2007).Crossref, Medline, CAS, Google Scholar
181 Mascher T, Helmann JD, Unden G: Stimulus perception in bacterial signal-transducing histidine kinases. Microbiol. Mol. Biol. Rev.70,910–938 (2006).Crossref, Medline, CAS, Google Scholar
182 Li M, Cha DJ, Lai Y, Villaruz AE, Sturdevant DE, Otto M: The antimicrobial peptide-sensing system aps of Staphylococcus aureus. Mol. Microbiol.66,1136–1147 (2007).Crossref, Medline, CAS, Google Scholar

Vol. 4, No. 2

Metrics

Downloaded 521 times

History

Published online 4 March 2009

Published in print March 2009

Information

Keywords

Acknowledgements

I would like to extend my apologies to GBS researchers whose work has not been reviewed here owing to space constraints. I thank Dr A Siegesmund, D Chaffin, J Karlinsey and all members of my laboratory for critical reading of this review.

Financial & competing interests disclosure

GBS research in L Rajagopal’s laboratory is supported by funding from the NIH/NIAID (grant no. R01A1070749), the Seattle Children’s Hospital Research Institute and the Deion Branch Athletic Foundation. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

PDF download

Understanding the regulation of Group B Streptococcal virulence factors

Abstract

Bibliography