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8 - Group A streptococcal invasion of host cells

Published online by Cambridge University Press:  21 August 2009

Harry S. Courtney
Research Service (151), Veterans Affairs Medical Center, Memphis, Tennessee 38104, USA
Andreas Podbielski
Department of Medical Microbiology & Hospital Hygiene, University Hospital Rostock, D-18057 Rostock, Germany
Richard J. Lamont
University of Florida
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Group A streptococci (GAS), Streptococcus pyogenes, are beta-hemolytic, Gram-positive, pyogenic cocci that usually grow in chains. S. pyogenes is classified as group A based on serological reactions with its C carbohydrate, which consists of polymers of rhamnose substituted with N-acetylglucosamine (Lancefield, 1933). For epidemiological purposes, GAS are further classified into more than 100 different types based on serological reactions with the variable domains of M proteins, or, more recently, based on 5′ emm gene sequences (Beall et al., 1996). Other typing schemes based on serological reactions with serum opacity factor, T proteins, and R proteins are also used (Johnson and Kaplan, 1993).

S. pyogenes is almost exclusively associated with humans and commonly causes a variety of diseases, including pharyngotonsillitis, impetigo, scarlet fever, and more severe infections, such as puerperal sepsis, myositis, necrotizing fasciitis, and toxic shock syndrome. Among several of the nonsuppurative complications of group A streptococcal infections are acute rheumatic fever and acute glomerulonephritis, which are usually preceded by infections of the throat and skin, respectively. These sequelae are thought to be due to autoimmune T-and B-cell responses induced by streptococcal products. Accumulating evidence also suggests that group A streptococcal infections may lead to other autoimmune diseases, such as obsessive compulsive disorders, or they may exacerbate others such as guttate psoriasis (reviewed by Cunningham, 2000).


To establish these infections, the streptococcus must first attach to the epithelium of the host.

Publisher: Cambridge University Press
Print publication year: 2004

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Abraham, S. N., Beachey, E. H., and Simpson, W. A. (1983). Adherence of Streptococcus pyogenes, Escherichia coli, and Pseudomonas aeruginosa to fibronectin-coated and uncoated epithelial cells. Infect. Immun. 41, 1261–1268Google ScholarPubMed
Akesson, P., Sjoholm, A. G., and Bjorck, L. (1996). Protein SIC, a novel extracellular protein of Streptococcus pyogenes interfering with complement function. J. Biol. Chem. 271, 1081–1088CrossRefGoogle ScholarPubMed
Ashbaugh, C., Moser, T., Shearer, M., White, G., Kennedy, R., and Wessels, M. (2000). Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection. Cell. Microbiol. 2, 283–292CrossRefGoogle Scholar
Beachey, E. H. and Ofek, I. (1976). Epithelial cell binding of group A streptococci by lipoteichoic acid on fimbriae denuded of M protein. J. Exp. Med. 143, 759–771CrossRefGoogle Scholar
Beall, B., Facklam, R., and Thompson, T. (1996). Sequencing emm-specific PCR products for routine and accurate typing of group A streptococci. J. Clin. Microbiol. 34, 953–958Google ScholarPubMed
Beckert, S., Kreikmeyer, B., and Podbielski, A. (2001). Group A streptococcal rofA gene is involved in the control of several virulence genes and eucaryotic cell attachment and internalization. Infect. Immun. 69, 534–537CrossRefGoogle Scholar
Beres, S., Sylva, G., Barbian, K., Lei, B., Hoff, J., Mammarella, N., Liu, M., Smoot, J., Porcella, S., Parkins, L., Campbell, D., Smith, T., McCormick, J., Leung, D., Schlievert, P., and Musser, J. M. (2002). Genome sequence of a serotype M3 strain of group A streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence. Proc. Natl Acad. Sci. USA 99, 10,078–10,083CrossRefGoogle ScholarPubMed
Berkower, C., Ravins, M., Moses, A., and Hanski, E. (1999). Expression of different group A streptococcal M proteins in an isogenic background demonstrates diversity in adherence to and invasion of eukaryotic cells. Mol. Microbiol. 31, 1463–1475CrossRefGoogle Scholar
Bisno, A. and Stevens, D. (2000). Streptococcus pyogenes (including streptococcal shock and necrotizing fasciitis). In Principles and Practice of Infectious Diseases, ed, Mandell, G., Bennet, J., and Dolin, R. pp. 2102–2117. Philadelphia, Churchill Livingstone
Botta, G. (1981). Surface components in adhesion of group A streptococci to pharyngeal epithelial cells. Curr. Microbiol. 6, 101–104CrossRefGoogle Scholar
Brandt, C., Allerberger, F., Spellerberg, B., Holland, R., Lutticken, R., and Haase, G. (2001). Characteristics of consecutive Streptococcus pyogenes isolates from patients with pharyngitis and bacteriological treatment failure: special reference to prtF1 and sic/drs. J. Infect. Dis. 183, 670–674CrossRefGoogle Scholar
Bretscher, A., Edwards, K., and Fehon, R. G. (2002). ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell. Biol. 3, 586–599CrossRefGoogle ScholarPubMed
Broudy, T., Pancholi, V., and Fischetti, V. (2001). Induction of lysogenic bacteriophage and phage-associated toxin from group A streptococci during co-culture with human pharyngeal cells. Infect. Immun. 69, 1440–1443CrossRefGoogle Scholar
Broudy, T., Pancholi, V., and Fischetti, V. (2002). The in vitro interaction of Streptococcus pyogenes with human pharyngeal cells induces a phage-encoded extracellular DNase. Infect. Immun. 70, 2805–2811CrossRefGoogle ScholarPubMed
Caparon, M., Stevens, D., Olsen, A., Scott, J. R. (1991). Role of M protein in adherence of group A streptococci. Infection and Immunity 59, 1811–7Google ScholarPubMed
Chaussee, M. S., Sylva, G. L., Sturdevant, D. E., Smoot, L. M., Graham, M. R., Watson, R. O., Musser, J. M. (2002). Rgg influences the expression of multiple regulatory loci to corregulate virulence factor expression in Streptococcus pyogenes. Infection and Immunity 70, 762–70CrossRefGoogle ScholarPubMed
Chaussee, M. S., Watson, R. O., Smoot, J. C., Musser, J. M. (2001). Identification of Rgg-regulated exoproteins of Streptococcus pyogenes. Infection and Immunity 69, 822–31CrossRefGoogle ScholarPubMed
Cheng, Q., Stafslien, D., Purushothaman, S., and Cleary, P. (2002). The group B streptococcal C5a peptidase is both a specific protease and invasin. Infect. Immun. 70, 2408–2413CrossRefGoogle Scholar
Cleary, P. and Cue, D. (2000). High frequency invasion of mammalian cells by β hemolytic streptococci. Subcell. Biochem. 33, 137–166CrossRefGoogle ScholarPubMed
Courtney, H. S., Bronze, M. S., Dale, J. B., and Hasty, D. L. (1994). Analysis of the role of M24 protein in group A streptococcal adhesion and colonization by use of ω-interposon mutagenesis. Infect. Immun. 62, 4868–4873Google Scholar
Courtney, H. S., Dale, J. B., and Hasty, D. L. (1996). Differential effects of the streptococcal fibronectin-binding protein, FBP54, on adhesion of group A streptococci to human buccal cells and HEp-2 tissue culture cells. Infect. Immun. 64, 2415–2419Google Scholar
Courtney, H. S., Hasty, D. L., and Dale, J. B. (2002). Molecular mechanisms of adhesion, colonization, and invasion of group A streptococci. Ann. Med. 34, 77–87CrossRefGoogle ScholarPubMed
Courtney, H. S., Hasty, D. L., Dale, J. B., and Poirier, T. P. (1992). A 28 kilodalton fibronectin-binding protein of group A streptococci. Curr. Microbiol. 25, 245–250CrossRefGoogle ScholarPubMed
Courtney, H. S., Liu, S., Dale, J. B., and Hasty, D. L. (1997a). Conversion of M serotype 24 of Streptococcus pyogenes to M serotypes 5 and 18: effect on resistance to phagocytosis and adhesion to host cells. Infect. Immun. 65, 2472–2474Google Scholar
Courtney, H. S., Ofek, I., Hasty, D. L. (1997b). M protein mediated adhesion of M type 24 Streptococcus pyogenes stimulates release of interleukin-6 by HEp-2 tissue culture cells. FEMS Microbiol. Lett. 151, 65–70CrossRefGoogle Scholar
Courtney, H. S., Ofek, I., Simpson, W. A., Hasty, D. L., and Beachey, E. H. (1986). Binding of Streptococcus pyogenes to soluble and insoluble fibronectin. Infect. Immun. 53, 454–459Google ScholarPubMed
Courtney, H. S., Hunolstein, C., Dale, J. B., Bronze, M. S., Beachey, E. H., and Hasty, D. L. (1992). Lipoteichoic acid and M protein: dual adhesins of group A streptococci. Microb. Pathog. 12, 199–208CrossRefGoogle Scholar
Cue, D., Dombek, P., Lam, H., and Cleary, P. (1998). Streptococcus pyogenes serotype M1 encodes multiple pathways for entry into human epithelial cells. Infect. Immun. 66, 4593–4601Google ScholarPubMed
Cunningham, M. (2000). Pathogenesis of group A streptococcal infections. Clin. Microbiol. Rev. 13, 470–511CrossRefGoogle ScholarPubMed
Cywes, C., Stamenkovic, I., and Wessels, M. R. (2000). CD44 as a receptor for colonization of the pharynx by group A streptococci. J. Clin. Invest. 106, 995–1002CrossRefGoogle Scholar
Cywes, C. and Wessels, M. (2001). Group A streptococcus tissue invasion by CD-44-mediated cell signalling. Nature 414, 648–652CrossRefGoogle ScholarPubMed
Darmstadt, G. L., Fleckman, P., and Rubens, C. E. (1999). Tumor necrosis factor-alpha and interleukin-1alpha decrease the adherence of Streptococcus pyogenes to cultured keratinocytes. J. Infect. Dis. 180, 1718–1721CrossRefGoogle ScholarPubMed
Darmstadt, G. L., Mentele, L., Podbielski, A., and Rubens, C. E. (2000). Role of group A streptococcal virulence factors in adherence to keratinocytes. Infect. Immun. 68, 1215–1221CrossRefGoogle Scholar
Dinkla, K., Rohde, M., Jansen, W., Carapetis, J., Chhatwal, G., and Talay, S. (2003). Streptococcus pyogenes recruits collagen via surface-bound fibronectin: a novel colonization and immune evasion mechanism. Mol. Microbiol. 47, 861–869CrossRefGoogle ScholarPubMed
Dinulos, J., Mentele, L., Fredericks, L., Dale, B., and Darmstadt, G. (2003). Keratinocyte expression of human β defensin 2 following bacterial infection: role in cutaneous host defense. Clin. Diagnost. Lab. Immunol. 10, 161–166Google ScholarPubMed
Dombek, P., Cue, D., Sedgewick, J., Ruschkowski, S., Finlay, B., and Cleary, P. (1999). High frequency intracellular invasion of epithelial cells by serotype M1 group A streptococci: M1 protein-mediated invasion and cytoskeletal rearrangements. Mol. Microbiol. 31, 859–70CrossRefGoogle Scholar
Dorschner, R., Pestonjamasp, V., Tamakuwala, S., Ohtake, T., Rudisill, J., Nizet, V., Agerberth, B., Gudmundsson, G., and Gallo, R. (2001). Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A streptococcus. J. Invest. Dermatol. 117, 91–97CrossRefGoogle ScholarPubMed
Duensing, T., Wing, J., and Putten, J. (1999). Sulfated polysaccharide-directed recruitment of mammalian host proteins: a novel strategy in microbial pathogenesis. Infect. Immun. 67, 4463–4468Google ScholarPubMed
Dunne, D. W., Resnick, D., Greenberg, D. J., Kreiger, J. M., and Joiner, K. A. (1994). The type 1 macrophage scavenger receptor binds to Gram-positive bacteria and recognizes lipoteichoic acid. Proc. Natl Acad. Sci. USA 91, 1863–1867CrossRefGoogle Scholar
Dunny, G. and Leonard, B. (1997). Cell-cell communication in gram-positive bacteria. Annu. Rev. Microbiol. 51, 527–564CrossRefGoogle ScholarPubMed
Elsner, A., Kreikmeyer, B., Braukn-Kiewnick, A., Spellerberg, B., Buttaro, B., and Podbielski, A. (2002). Involvement of Lsp, a member of the LraI-lipoprotein family in Streptococcus pyogenes, in eukaryotic cell adhesion and internalization. Infect. Immun. 70, 4859–4869CrossRefGoogle ScholarPubMed
Ferretti, J., McShan, W., Ajdic, D., Savic, D., Savic, G., Lyon, K., Primeaux, C., Sezate, S.Suvorov, A., Kenton, S., Lai, H. S., Lin, S. P., Qian, Y., Jia, H. G., Najar, F. Z., Ren, Q., Zhu, N., Song, L., White, J., Yuan, X., Clifton, S. W., Roe, B. A. and McLaughlin, R. (2001). Complete genome sequence of an M1 strain of Streptococcus pyogenes. Proc. Natl Acad. Sci. USA 98, 4658–4663CrossRefGoogle ScholarPubMed
Fischetti, V. A. (1989). Streptococcal M protein: molecular design and biological behaviour. Clin. Microbiol. 2, 285–314CrossRefGoogle Scholar
Fluckiger, U., Jones, K., and Fischetti, V. (1998). Immunoglobulins to group A streptococcal surface molecules decrease adherence to and invasion of human pharyngeal cells. Infect. Immun. 66, 974–979Google Scholar
Fogg, G. C. and Caparon, M. G. (1997). Constitutive expression of fibronectin binding in Streptococcus pyogenes as a result of anaerobic activation of rofA. J. Bacteriol. 179, 6172–6180CrossRefGoogle ScholarPubMed
Frick, I., Morgelin, M., and Bjorck, L. (2000). Virulent aggregates of Streptococcus pyogenes are generated by homophillic protein-protein interactions. Mol. Microbiol. 37, 1232–1247CrossRefGoogle Scholar
Gerlach, D., Schalen, C., Tigyi, Z., Nilsson, B., Forsgren, A., and Naidu, A. S. (1994). Identification of a novel lectin in Streptococcus pyogenes and its possible role in bacterial adherence to pharyngeal cells. Curr. Microbiol. 28, 331–338CrossRefGoogle Scholar
Gibson, C., Fogg, G., Okada, N., Geist, R. T., Hanski, E., and Caparon, M. (1995). Regulation of host cell recognition in Streptococcus pyogenes. Dev. Biol. Stand. 85, 137–144Google ScholarPubMed
Grabovskaya, K. B., Totolian, A., Ryc, M., Havlicek, J., Burova, L., Bicova, R. (1980). Adherence of group A streptococci to epithelial cells in tissue culture. Zentral Bakteriol Mikrobiol Hyg [A] 247, 303–314Google Scholar
Granok, A., Parsonage, D., Ross, R., and Caparon, M. (2000). The RofA binding site in Streptococcus pyogenes is utilized in multiple transcriptional pathways. J. Bacteriol. 182, 1529–1540CrossRefGoogle ScholarPubMed
Gryllos, I., Cywes, C., Shearer, M., Cary, M., Kennedy, R., and Wessels, M. (2001). Regulation of capsule gene expression by group A streptococcus during pharyngeal colonization and invasive infection. Mol. Microbiol. 42, 61–74CrossRefGoogle ScholarPubMed
Hanski, E. and Caparon, M. (1992). Protein F, a fibronectin-binding protein, is an adhesin of the group A streptococcus, Streptococcus pyogenes. Proc. Natl Acad. Sci. USA 89, 6172–6176CrossRefGoogle Scholar
Hartas, J. and Sriprakash, K. (1999). Streptococcus pyogenes strains containing emm12 and emm55 possess a novel gene coding for distantly related SIC protein. Microb. Pathogen. 26, 25–33CrossRefGoogle ScholarPubMed
Hasty, D. L., Ofek, I., Courtney, H. S., and Doyle, R. (1992). Multiple adhesins of streptococci. Infect. Immun. 60, 2147–2152Google ScholarPubMed
Heath, A., DiRita, V., Barg, N., and Engleberg, N. C. (1997). A two-component regulatory system, CsrR-CsrS, represses expression of three Streptococcus pyogenes virulence factors, hyaluronic acid capsule, streptolysin S, and pyrogenic exotoxin B. Infect. Immun. 67, 5298–5305Google Scholar
Hidalgo-Grass, C., Ravins, M., Dan-Goor, M., Jaffe, J., Moses, A., and Hanski, E. (2002). A locus of group A streptococci involved in invasive disease and DNA transfer. Mol. Microbiol. 46, 87–99CrossRefGoogle Scholar
Hoe, N., Ireland, R., DeLeo, F., Gowen, B., Dorward, D., Voyich, J., Liu, M., Burns, E. Jr., Culnan, D., Bretscher, A., and Musser, J. M. (2002). Insight into the molecular basis of pathogen abundance: group A streptococcus inhibitor of complement inhibits bacterial adherence and internalization into human cells. Proc. Natl Acad. Sci. USA 99, 7646–7651CrossRefGoogle ScholarPubMed
Hynes, R. O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110, 673–687CrossRefGoogle ScholarPubMed
Hytonen, J., Haataja, S., and Finne, J. (2003). Streptococcus pyogenes glycoprotein-binding strepadhesin activity is mediated by a surface-associated carbohydrate-degrading enzyme, pullanase. Infect. Immun. 71, 784–793CrossRefGoogle Scholar
Hytonen, J., Haataja, S., Gerlach, D., Podbielski, A., and Finne, J. (2001). The speB virulence factor of Streptococcus pyogenes, a multifunctional secreted and cell surface molecule with strepadhesin, laminin-binding and cysteine protease activity. Mol. Microbiol. 39, 512–519CrossRefGoogle ScholarPubMed
Jadoun, J., Burstein, E., Hanski, E., and Sela, S. (1997). Proteins M6 and F1 are required for efficient invasion of group A streptococci into cultured epithelial cells. Adv. Exp. Med. 418, 511–515CrossRefGoogle Scholar
Jadoun, J., Eyal, O., and Sela, S. (2002). Role of CsrR, hyaluronic acid, and SpeB in the internalization of Streptococcus pyogenes M type 3 strain by epithelial cells. Infect. Immun. 70, 462–469CrossRefGoogle ScholarPubMed
Jadoun, J. and Sela, S. (2000). Mutation in csrR global regulator reduces Streptococcus pyogenes internalization. Microb. Pathogen. 29, 311–317CrossRefGoogle ScholarPubMed
Jaffe, J., Natanson-Yaron, S., Caparon, M., and Hanski, E. (1996). Protein F2, a novel fibronectin-binding protein from Streptococcus pyogenes, possesses two binding domains. Mol. Microbiol. 21, 373–384CrossRefGoogle ScholarPubMed
Jeng, A., Sakota, V., Li, Z., Datta, V., Beall, B., and Nizet, V. (2003). Molecular genetic analysis of a group A streptococcus operon encoding serum opacity factor and a novel fibronectin-binding protein, SfbX. J. Bacteriol. 185, 1208–1217CrossRefGoogle Scholar
Ji, Y., Schnitzler, N., DeMaster, E., and Cleary, P. (1998). Impact of M49, Mrp, Enn, and C5a peptidase proteins of colonization of the mouse oral mucosa by Streptococcus pyogenes. Infect. Immun. 66, 5399–5405Google ScholarPubMed
Johnson, D. and Kaplan, E. (1993). A review of the correlation of T-agglutination patterns and M-protein typing and opacity factor production in the identification of group A streptococci. J. Med. Microbiol. 38, 311–315CrossRefGoogle ScholarPubMed
Kallman, J. and Kihlstrolm, E. (1997). Penetration of group B streptococci through polarized Madin-Darby canine kidney cells. Ped. Res. 42, 799–804CrossRefGoogle Scholar
Kreikemeyer, B., Boyle, M., Buttaro, B., Heinemann, M., and Podbielski, A. (2001). Group A streptococcal growth-phase associated virulence factor regulation by a novel operon (Fas) with homologies to two-component-type regulators requires a small RNA molecule. Mol. Microbiol. 39, 392–406CrossRefGoogle Scholar
Kreikemeyer, B., Darmstadt G., Reichard, W., Mentele, L., Susa, M., Podbielski, A. (2003) Biological consequences of the Streptococcus pyogenes two-component regulator Fas activity on host cell adherence, internalizaton, and apoptosis. Submitted
Kreikemeyer, B., McIver, K., and Podbielski, A. (2003). Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen-host interactions. Trends Microbiol. 11, 224–232CrossRefGoogle ScholarPubMed
Kreikemeyer, B., Talay, S. R., and Chhatwal, G. S. (1995). Characterization of a novel fibronectin-binding surface protein in group A streptococci. Mol. Microbiol. 17, 137–145CrossRefGoogle ScholarPubMed
Lancefield, R. C. (1933). A serological differentiation in human and other groups of hemolytic streptococci. J. Exp. Med. 57, 571–595CrossRefGoogle ScholarPubMed
LaPenta, D., Rubens, C., Chi, E., and Cleary, P. (1994). Group A streptococci efficiently invade human respiratory epithelial cells. Proc. Natl Acad. Sci. USA 91, 12,115–12,119CrossRefGoogle Scholar
Lei, B., Deleo, F., Reid, S., Voyich, J., Magoun, L., Liu, M., Braughton, K., Ricklefs, S., Hoe, N., Cole, R. L., Leong, J. M., Musser, J. M. (2002). Opsonophagocytosis-inhibiting Mac protein of group A streptococcus: identification and characteristics of two genetic complexes. Infect. Immun. 70, 6880–6890CrossRefGoogle ScholarPubMed
Lin, C., Kuan, I., Wang, C., Lee, H., Lee, W., Sheu, J., Hsiao, G., Wu, C. and Kuo, H. (2002). Lipoteichoic acid-induced cyclooxygenase-2 expression requires activation of p44/42 and p38 mitogen-activated protein kinase signal pathways. Eur. J. Pharmacol. 450, 1–9CrossRefGoogle ScholarPubMed
Lukomski, S., Nakashima, K., Abdi, I., Cipriano, V., Ireland, R., Reid, S., Adams, G., Musser, J. M. (2000). Identification and characterization of scl gene encoding a group A streptococcus extracellular protein virulence factor with similarity to human collagen. Infection and Immunity 68, 6542–6553CrossRefGoogle ScholarPubMed
Lukomski, S., Nakashima, K., Abdi, I., Cipriano, V., Shelvin, B., Graviss, E., and Musser, J. (2001). Identification of characterization of a second extracellular collagen-like protein made by group A streptococcus: control of production at the level of transcription. Infect. Immun. 69, 1729–1738CrossRefGoogle Scholar
Madden, J., Ruiz, N., and Caparon, M. (2001). Cytolysin-mediated translocation (CMT): a functional equivalent of type III secretion in gram-positive bacteria. Cell 104, 143–152CrossRefGoogle ScholarPubMed
Mandell, G., Bennet, J., Dolin, R. (ed) (2000) In Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Philadelphia, Churchill Livingstone. pp-2101–2117
McIver, K. S., Heath, A. S., and Scott, J. R. (1995). Regulation of virulence by environmental signals in group A streptococci: influence of osmolarity, temperature, gas exchange, and iron limitation on emm transcription. Infect. Immun. 63, 4540–4542Google Scholar
McIver, K. S. and Scott, J. R. (1997). Role of mga in growth phase regulation of virulence genes of the group A streptococcus. J. Bacteriol. 179, 5178–5187CrossRefGoogle ScholarPubMed
McLandsborough, L., Cleary, P. P. (1995). Insertional inactivation of virR in Streptococcus pyogenes M49 demonstrates that VirR functions as a positive regulator of ScpA, FcRA, OF, and M protein. FEMS Microbiological Letters 128, 45–51CrossRefGoogle ScholarPubMed
Medina, E., Anders, D., and Chhatwal, G. S. (2002). Induction of NF-kappaB nuclear translocation in human respiratory epithelial cells by group A streptococci. Microbiol. Pathog. 33, 307–313CrossRefGoogle ScholarPubMed
Miettinen, M., Matikainen, S., Vuopio-Varjkila, J., Pirhonen, J., Varkila, K., Kurimoto, M., and Julkunen, I. (1998). Lactobacilli and streptococci induce interleukin-12 (IL-12), IL-18, and gamma interferon production in human periphereal blood mononuclear cells. Infect. Immun. 66, 6058–6062Google Scholar
Molinari, G., Rohde, M., Guzman, C., and Chhatwal, G. (2000). Two distinct pathways for the invasion of streptococci in non-phagocytic cells. Cell. Microbiol. 2, 145–154CrossRefGoogle Scholar
Molinari, G., Rohde, M., Talay, S. R., Chhatwal, G. S., Beckert, S., and Podbielski, A. (2001). The role played by the group A streptococcal negative regulator Nra on bacterial interactions with epithelial cells. Mol. Microbiol. 40, 99–114CrossRefGoogle Scholar
Molinari, G., Talay, S. R., Valentin-Weigand, P., Rohde, M., and Chhatwal, G. (1997). The fibronectin-binding protein of Streptococcus pyogenes, Sfbl, is involved in internalization of group A streptococci by epithelial cells. Infect. Immun. 65, 1357–1363Google Scholar
Nakagawa, I., Nakata, M., Kawabata, S., and Hamada, S. (2001). Cytochrome C-mediated caspase-9 activation triggers apoptosis in Streptococcus pyogenes infected epithelial cells. Cell. Microbiol. 3, 359–405CrossRefGoogle ScholarPubMed
Natanson, S., Sela, S., Moses, A., Musser, J., Caparon, M., and Hanski, E. (1995). Distribution of fibronectin-binding proteins among group a streptococci of different M types. J. Infect. Dis. 171, 871–878CrossRefGoogle Scholar
Neeman, R., Keller, N., Barzilai, A., Korenman, Z., and Sela, S. (1998). Prevalence of internalization-associated gene, prtF1, among persisting group-A streptococcus strains isolated from asymptomatic carriers. Lancet 352, 1974–1977CrossRefGoogle Scholar
Nizet, V., Ohtake, T., Lauth, X., Trowbridge, J., Rudisill, , J., Dorschner, R., Pestonjamasp, V., Piraino, J., Huttner, K., and Gallo, R. L. (2001). Innate antimicrobial peptide protects the skin from invasive bacterial infections. Nature 414, 454–457CrossRefGoogle Scholar
Ofek, I., Zafiri, I., Goldhar, J., and Eisenstein, B. (1990). Inability of toxin inhibitors to neutralize enhanced toxicity caused by bacteria adherent to tissue culture cells. Infect. Immun. 58, 3737–3742Google ScholarPubMed
Okada, N., Liszewski, M., Atkinson, J., and Caparon, M. (1995). Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus. Proc. Natl Acad. Sci. USA 92, 2489–2493CrossRefGoogle Scholar
Okada, N., Pentland, A., Falk, P., and Caparon, M. (1994). M protein and protein F act as important determinants of cell-specific tropism of Streptococcus pyogenes in skin tissue. J. Clin. Invest. 94, 965–977CrossRefGoogle ScholarPubMed
Okada, N., Tatsuno, I., Hanski, E., Caparon, M., and Sasakawa, C. (1998). Streptococcus pyogenes protein F promotes invasion of HeLa cells. Microbiology 144, 3079–3086CrossRefGoogle ScholarPubMed
Okahashi, N., Sakurai, A., Nakagawa, I., Fujiwara, T., Kawabata, S., Amano, A. and Hamada, S. (2003). Infection by Streptococcus pyogenes induces the receptor activator of NF-kB ligand expression in mouse osteoblastic cells. Infect. Immun. 71, 948–955CrossRefGoogle Scholar
Osterlund, A. and Engstrand, L. (1997). An intracellular sanctuary for Streptococcus pyogenes in human tonsillar epithelium – studies of asymptomatic carriers and in vitro cultured biopsies. Acta Otolaryngol. 117, 883–888CrossRefGoogle ScholarPubMed
Osterlund, A., Popa, R., Nikkila, T., Scheynius, A., and Engstrand, L. (1997). Intracellular reservoir of Streptococcus pyogenes in vivo: a possible explanation for recurrent pharyngotonsillitis. Laryngoscope 107, 640–646CrossRefGoogle ScholarPubMed
Ozeri, V., Rosenshine, I., Mosher, D., Fassler, R., and Hanski, E. (1998). Roles of integrins and fibronectin in the entry of Streptococcus pyogenes into cells via protein F1. Mol. Microbiol. 30, 625–637CrossRefGoogle ScholarPubMed
Pancholi, V. and Fischetti, V. (1992). A major surface protein on group A streptococci glyceraldehyde-3-phosphate-dehydrogenase with multiple binding activity. J. Exp. Med. 176, 415–426CrossRefGoogle Scholar
Pancholi, V. and Fischetti, V. (1997). Regulation of the phosphorylation of human pharyngeal cell proteins by group A streptococcal surface dehydrogenase: signal transduction between streptococci and pharyngeal cells. J. Exp. Med. 186, 1633–1643CrossRefGoogle Scholar
Perez-Casal, J., Caparon, M., and Scott, J. (1991). Mry, a trans-acting positive regulator of the M protein gene with similarity to the receptor proteins of two-component regulatory systems. J. Bacteriol. 173, 2617–2624CrossRefGoogle Scholar
Perez-Casal, J., Okada, N., Caparon, M., and Scott, J. (1995). Role of the conserved C-repeat region of the M protein of Streptococcus pyogenes. Mol. Microbiol. 15, 907–916CrossRefGoogle Scholar
Podbielski, A., Beckert, S., Schattke, R., Leithauser, F., Lestin, F., Gobler, B., and Kreikemeyer, B. (2003). Epidemiology and virulence gene expression of intracellular group A streptococci in tonsils of recurrently infected adults. Int. J. Med. Microbiol. 293, 179–190CrossRefGoogle Scholar
Podbielski, A., Woischnik, M., Leonard, B., and Schmidt, K. (1999). Characterization of nra, a global negative regulator gene in group A streptococci. Mol. Microbiol. 31, 1051–1064CrossRefGoogle ScholarPubMed
Podbielski, A, Woischnik, M., Pohl, B., and Schmidt, K. H. (1996). What is the size of the group A streptococcal vir regulon? The Mga regulator affects expression of secreted and surface virulence factors. Med. Microbiol. Immunol. 185, 171–181CrossRefGoogle Scholar
Pritchard, K. and Cleary, P. (1996). Differential expression of genes in the vir regulon of Streptococcus pyogenes is controlled by transcription termination. Mol. Gen. Genet. 250, 207–213Google ScholarPubMed
Rakonjac, J. V., Robbins, J. C., and Fischetti, V. (1995). DNA sequence of the serum opacity factor of group A streptococci: identification of a fibronectin-binding repeat domain. Infect. Immun. 63, 622–631Google Scholar
Rasmussen, M. and Bjorck, L. (2001). Unique regulation of SclB – a novel collagen-like surface protein of Streptococcus pyogenes. Mol. Microbiol. 40, 1427–1438CrossRefGoogle ScholarPubMed
Rasmussen, M., Eden, A., and Bjorck, L. (2000). SclA, a novel collagen-like surface protein of Streptococcus pyogenes. Infect. Immun. 68, 6370–6377CrossRefGoogle ScholarPubMed
Rocha, C. and Fischetti, V. (1999). Identification and characterization of a novel fibronectin-binding protein on the surface of group A streptococci. Infect. Immun. 67, 2720–2728Google ScholarPubMed
Rodhe, M., Muller, E., Chhatwal, G., and Talay, S. (2003). Host cell caveolae act as an entry port for group A streptococci. Cell. Microbiol. 5, 323–342Google Scholar
Ruiz, N., Wang, B., Pentland, A., and Caparon, M. (1998). Streptolysin O and adherence synergistically modulate proinflammatory responses of keratinocytes to group A streptococci. Mol. Microbiol. 27, 337–346CrossRefGoogle ScholarPubMed
Ryan, P., Pancholi, V., and Fischetti, V. (2001). Group A streptococci bind to mucin and human pharyngeal cells through sialic acid-containing receptors. Infect. Immun. 69, 7402–7412CrossRefGoogle Scholar
Saetre, T., Hoiby, E., Kahler, H., and Lyberg, T. (2000). Changed expression of leukocyte adhesion molecules and increased production of reactive oxygen species caused by Streptococcus pyogenes in human whole blood. APMIS 108, 573–580CrossRefGoogle ScholarPubMed
Sanford, B. A., Davison, V. E., Ramsay, M. A. (1982). Fibrinogen-mediated adherence of group A streptococci to influenza A virus-infected cells. Infection and Immunity 38, 513–520Google Scholar
Schmidt, K. H., Mann, K., Cooney, J., and Kohler, W. (1993). Multiple binding of type 3 streptococcal M protein to fibrinogen, albumin, and fibronectin. FEMS Immun. Med. Microbiol. 7, 135–144CrossRefGoogle ScholarPubMed
Schrager, H. M., Alberti, S., Cywes, S., Dougherty, G. J., and Wessels, M. R. (1998). Hyaluronate acid capsule modulates M protein mediated adherence and acts as a ligand for attachment of group A streptococci to CD44 on human keratinocytes. J. Clin. Invest. 101, 1708–1716CrossRefGoogle Scholar
Sela, S., Aviv, A., Tovi, A., Burstein, I., Caparon, M., and Hanski, E. (1993). Protein F: an adhesin of Streptococcus pyogenes binds fibronectin via two distinct domains. Mol. Microbiol. 10, 1049–1055CrossRefGoogle ScholarPubMed
Sierig, G., Cywes, C., Wessels, M., and Ashbaugh, C. (2003). Cytotoxic effects of streptolysin O and streptolysin S enhance the virulence of poorly encapsulated group A streptococci. Infect. Immun. 71, 446–455CrossRefGoogle ScholarPubMed
Simpson, W. A. and Beachey, E. H. (1983). Adherence of group A streptococci to fibronectin on oral epithelial cells. Infect. Immun. 39, 275–279Google Scholar
Smoot, J., Barbian, K., Gompel, J., Smoot, L., Chaussee, M., Sylva, G., Sturdevant, D., Ricklefs, S., Porcella, S. F., Parkins, C. D., Beres, S. B., Campbell, D. S., Smith, T. M., Zhang, Q., Kapur, V., Daly, J. A., Veasy, L. G., and Musser, J. M., (2002). Genome sequences and comparative microarray analysis of serotype M18 group A streptococcus strains associated with acute rheumatic fever outbreaks. Proc. Natl Acad. Sci.USA 99, 4668–4673CrossRefGoogle ScholarPubMed
Speck, O., Hughes, S., Noren, N., Kulikauskas, R., and Fehon, R. (2003). Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity. Nature 421, 83–87CrossRefGoogle ScholarPubMed
Stalhammar-Carlemalm, M., Areschoug, T., Larsson, C., and Lindahl, G. (1999). The R28 protein of Streptococcus pyogenes is related to se eral group B streptococcal surface proteins, confers protective immunity and promotes binding to human epithelial cells. Mol. Microbiol. 33, 208–219CrossRefGoogle Scholar
Stenfors, L., Bye, H., Raisanen, S., and Myklebust, R. (2000). Bacterial penetration into tonsillar surface epithelium during infectious mononucleosis. J. Laryngol. Otol. 114, 848–852Google ScholarPubMed
Stevens, D., Salmi, D., McIndoo, E., and Bryant, A. (2000). Molecular epidemiology of nga and NAD glycohydralase/ADP-ribosyltransferase activity among Streptococcus pyogenes causing toxic shock syndrome. J. Infect. Dis. 182, 1117–1128CrossRefGoogle Scholar
Stockbauer, K. E., Magoun, L., Liu, M., Burns, E. H. Jr., Gubbam, S., Renish, S., Pan, X., Bodary, S. C., Baker, E., Coburn, J., Leong, J. M., and Musser, J. M. (1999). A natural variant of the cysteine protease virulence factor of group A streptococcus with an arginine-glycine-aspartic acid (RGD) motif preferentially binds human integrins αⅴβ3 and αIIbβ3. Proc. Natl Acad. Sci. USA 96, 242–247CrossRefGoogle Scholar
Talay, S. R., Valentin-Weigand, P., Jerlstrom, P. G., Timmis, K. N., and Chhatwal, G. S. (1993). Fibronectin-binding protein of Streptococcus pyogenes: sequence of the binding domain involved in adherence of streptococci to epithelial cells. Infect. Immun. 60, 3837–3844Google Scholar
Talay, S. R., Zock, A., Rohde, M., Molinari, G., Oggioni, M., Pozzi, G., Guzman, C. A., and Chhatwal, G. S. (2000). Co-operative binding of human fibronectin to Sfb1 protein triggers streptococcal invasion into respiratory epithelial cells. Cell. Microbiol. 2, 521–535CrossRefGoogle Scholar
Talay, S., Ehrenfeld, E., Chhatwal, G., and Timmis, K. (1991). Expression of the fibronectin-binding components of Streptococcus pyogenes in Escherichia coli demonstrates that they are proteins. Mol. Microbiol. 5, 1727–1734CrossRefGoogle ScholarPubMed
Tamura, G. and Nittayajarn, A. (2000). Group B streptococci and other gram-positive cocci bind to cytokeratin 8. Infect. Immun. 68, 2129–2134CrossRefGoogle Scholar
Terao, Y., Kawabata, S., Kunitomo, E., Murakami, J., Nakagawa, I., and Hamada, S. (2001). Fba, a novel fibronectin-binding protein from Streptococcus pyogenes, promotes bacterial entry into epithelial cells, and the fba gene is positively transcribed under the Mga regulator. Mol. Microbiol. 42, 75–86CrossRefGoogle ScholarPubMed
Terao, Y., Kawabata, S., Nakata, M., Nakagawa, I., and Hamada, S. (2002). Molecular characterization of a novel fibronectin-binding protein of Streptococcus pyogenes strains isolated from toxic shock-like syndrome patients. J. Biol. Chem. 277, 47,428–47,435CrossRefGoogle ScholarPubMed
Terao, Y., Kawabata, S., Kunitomo, E., Nakagawa, I., and Hamada, S. (2002). Novel laminin-binding protein of Streptococcus pyogenes, Lbp, is involved in adhesion to epithelial cells. Infect. Immun. 70, 993–997Google ScholarPubMed
Tomasini-Johansson, B., Kaufman, N., Ensenberger, M., Ozeri, V., Hanski, E., and Mosher, D. (2001). A 49-residue peptide from adhesin F1 of Streptococcus pyogenes inhibits fibronectin-matrix assembly. J. Biol. Chem. 276, 23,430–23,439CrossRefGoogle ScholarPubMed
Tsai, P., Lin, Y., Kuo, C., Lei, H., and Wu, J. (1999). Group A streptococcus induces apoptosis in human epithelial cells. Infect. Immun. 67, 4334–4339Google ScholarPubMed
Upton, M., Tagg, J. R., Wescombe, P., and Jenkinson, H. F. (2001). Intra-and interspecies signalling between Streptococcus salivarius and Streptococcus pyogenes mediated by SalA and SalA1 lantibiotic peptides. J. Bacteriol. 183, 3931–3938CrossRefGoogle Scholar
Valentin-Wiegand, P., Grulich-Henn, J., Chhatwal, G., Muller-Berhasus, G., Blobel, H., and Preissner, K. (1988). Mediation of adherence of streptococci to human endothelial cells by complement S protein (vitronectin). Infect. Immun. 56, 2851–2855Google Scholar
Visai, L., Bozzini, S., Raucci, G., Toniolo, A., and Speziale, P. (1995). Isolation and characterization of a novel collagen-binding protein from Streptococcus pyogenes strain 6414. J. Biol. Chem. 270, 347–353CrossRefGoogle ScholarPubMed
von Hunolstein, C., Greco, R., Ajello, M., Orefici, G., and Valenti, P. (2000). Streptococcus pyogenes internalization by Hela cells is not mediated by M6 protein. In Streptococci and Streptococcal Diseases – Entering the New Millennium, ed. D. Martin and J. Tagg, pp. 681–683, Wellington, New Zealand: Securacopy
Pawel-Rammingen, U., Johansson, B., and Bjorck, L. (2002). IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G. EMBO J. 21, 1607–1615CrossRefGoogle Scholar
Voyich, J., Sturdevant, D., Braughton, K., Kobayashi, S., Lei, B., Virtaneva, K., Dorward, D., Musser, J., and Deleo, F. (2003). Genome-wide protective response used by group A streptococcus to evade destruction by human polymorphonuclear leukocytes. Proc. Natl Acad. Sci. USA 100, 1996–2001CrossRefGoogle ScholarPubMed
Wadstrom, T. and Tylewska, S. (1982). Glycoconjugates as possible receptors for Streptococcus pyogenes. Curr. Microbiol. 7, 343–346CrossRefGoogle Scholar
Wang, B., Ruiz, N., Pentland, A., and Caparon, M. (1997). Keratinocyte proinflammatory responses to adherent and nonadherent group A streptococci. Infect. Immun. 65, 2119–2126Google ScholarPubMed
Wang, J. and Stinson, M. (1994). M protein mediates streptococcal adhesion to HEp-2 cells. Infection and Immunity 62, 442–448Google ScholarPubMed
Wang, J. and Stinson, M. (1994). Streptococcal M6 protein binds to fucose-containing glycoproteins on cultured human epithelial cells. Infect. Immun. 62, 1268–1274Google ScholarPubMed
Wessels, M. R. and Bronze, M. S. (1994). Critical role of the group A streptococcal capsule in pharyngeal colonization and infection in mice. Proc. Natl Acad. Sci. USA 91, 12,238–12,242CrossRefGoogle Scholar
Whatmore, A. M. (2001). Streptococcus pyogenes sclB encodes a putative hypervariable surface protein with a collagen-like repetitive structure. Microbiology 147, 419–429CrossRefGoogle ScholarPubMed
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