Streptococcus pyogenes adhesion and colonization

FEBS Letters

Volumn 590, Issue 21, 2016, Pages 3739-3757

  Brouwer, Stephan ^a   Barnett, Timothy C ^a   Rivera Hernandez, Tania ^a   Rohde, Manfred ^b   Walker, Mark J ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

Author keywords

adherence; biofilm; colonization; pathogenesis; Streptococcus pyogenes; transcriptional regulation

Indexed keywords

ADHESIN; BACTERIAL PROTEIN; BACTERIAL TOXIN; COLLAGEN; ENOLASE; EXOTOXIN B; FIBRONECTIN BINDING PROTEIN; HEMOPROTEIN RECEPTOR; M PROTEIN; OXIDOREDUCTASE; PHOSPHOLIPASE A2; PROTEIN FBP54; SORTASE; UNCLASSIFIED DRUG;

BACTERIAL COLONIZATION; BACTERIAL TRANSMISSION; BACTERIUM ADHERENCE; BACTERIUM PILUS; BIOFILM; CELL INVASION; HOST CELL; HOST PATHOGEN INTERACTION; HUMAN; MICROFLORA; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; QUORUM SENSING; REVIEW; STREPTOCOCCUS GROUP A; STREPTOCOCCUS PYOGENES; TRANSCRIPTION REGULATION; METABOLISM; MICROBIOLOGY; PHYSIOLOGY; RESPIRATORY SYSTEM; SKIN; STREPTOCOCCUS INFECTION; TRANSMISSION;

BACTERIAL ADHESION; BACTERIAL PROTEINS; BIOFILMS; HUMANS; RESPIRATORY SYSTEM; SKIN; STREPTOCOCCAL INFECTIONS; STREPTOCOCCUS PYOGENES;

EID: 84979017217     PISSN: 00145793     EISSN: 18733468     Source Type: Journal    
DOI: 10.1002/1873-3468.12254     Document Type: Review

References (210)

1. Carapetis JR, Steer AC, Mulholland EK and Weber M (2005) The global burden of group A streptococcal diseases. Lancet Infect Dis 5, 685–694.
2. Tse H, Bao JYJ, Davies MR, Maamary P, Tsoi H-W, Tong AHY, Ho TCC, Lin C-H, Gillen CM, Barnett TC et al. (2012) Molecular characterization of the 2011 Hong Kong scarlet fever outbreak. J Infect Dis 206, 341–351.
3. Ben Zakour NL, Davies MR, You Y, Chen JHK, Forde BM, Stanton-Cook M, Yang R, Cui Y, Barnett TC, Venturini C et al. (2015) Transfer of scarlet fever-associated elements into the group A Streptococcus M1T1 clone. Sci Rep 5, 15877.
4. Davies MR, Holden MT, Coupland P, Chen JHK, Venturini C, Barnett TC, Zakour NLB, Tse H, Dougan G, Yuen K-Y et al. (2015) Emergence of scarlet fever Streptococcus pyogenes emm12 clones in Hong Kong is associated with toxin acquisition and multidrug resistance. Nat Genet 47, 84–87.
5. Aziz RK and Kotb M (2008) Rise and persistence of global M1T1 clone of Streptococcus pyogenes. Emerg Infect Dis 14, 1511–1517.
6. Albrich WC, Monnet DL and Harbarth S (2004) Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes. Emerg Infect Dis 10, 514–517.
7. Walker MJ, Barnett TC, McArthur JD, Cole JN, Gillen CM, Henningham A, Sriprakash KS, Sanderson-Smith ML and Nizet V (2014) Disease manifestations and pathogenic mechanisms of group A Streptococcus. Clin Microbiol Rev 27, 264–301.
8. Walker MJ, Hollands A, Sanderson-Smith ML, Cole JN, Kirk JK, Henningham A, McArthur JD, Dinkla K, Aziz RK, Kansal RG et al. (2007) DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection. Nat Med 13, 981–985.
9. Courtney HS, Hasty DL and Dale JB (2002) Molecular mechanisms of adhesion, colonization, and invasion of group A streptococci. Ann Med 34, 77–87.
10. Nobbs AH, Lamont RJ and Jenkinson HF (2009) Streptococcus adherence and colonization. Microbiol Mol Biol Rev 73, 407–450.
11. Moschioni M, Pansegrau W and Barocchi MA (2010) Adhesion determinants of the Streptococcus species. Microb Biotechnol 3, 370–388.
12. Rohde M and Chhatwal GS (2013) Adherence and invasion of streptococci to eukaryotic cells and their role in disease pathogenesis. Curr Top Microbiol Immunol 368, 83–110.
13. Nobbs AH, Jenkinson HF and Everett DB (2015) Generic determinants of Streptococcus colonization and infection. Infect Genet Evol 33, 361–370.
14. Molinari G, Talay SR, Valentin-Weigand P, Rohde M and Chhatwal GS (1997) The fibronectin-binding protein of Streptococcus pyogenes, SfbI, is involved in the internalization of group A streptococci by epithelial cells. Infect Immun 65, 1357–1363.
15. Talay SR, Zock A, Rohde M, Molinari G, Oggioni M, Pozzi G, Guzman CA and Chhatwal GS (2000) Co-operative binding of human fibronectin to Sfbl protein triggers streptococcal invasion into respiratory epithelial cells. Cell Microbiol 2, 521–535.
16. Jadoun J, Ozeri V, Burstein E, Skutelsky E, Hanski E and Sela S (1998) Protein F1 is required for efficient entry of Streptococcus pyogenes into epithelial cells. J Infect Dis 178, 147–158.
17. Rohde M, Muller E, Chhatwal GS and Talay SR (2003) Host cell caveolae act as an entry-port for group A streptococci. Cell Microbiol 5, 323–342.
18. Akiyama H, Morizane S, Yamasaki O, Oono T and Iwatsuki K (2003) Assessment of Streptococcus pyogenes microcolony formation in infected skin by confocal laser scanning microscopy. J Dermatol Sci 32, 193–199.
19. Roberts AL, Connolly KL, Kirse DJ, Evans AK, Poehling KA, Peters TR and Reid SD (2012) Detection of group A Streptococcus in tonsils from pediatric patients reveals high rate of asymptomatic streptococcal carriage. BMC Pediatr 12, 3.
20. Fiedler T, Köller T and Kreikemeyer B (2015) Streptococcus pyogenes biofilms-formation, biology, and clinical relevance. Front Cell Infect Microbiol 5, 15.
21. Kreikemeyer B, McIver KS and Podbielski A (2003) Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen–host interactions. Trends Microbiol 11, 224–232.
22. Kreikemeyer B, Klenk M and Podbielski A (2004) The intracellular status of Streptococcus pyogenes: role of extracellular matrix-binding proteins and their regulation. Int J Med Microbiol 294, 177–188.
23. Patenge N, Fiedler T and Kreikemeyer B (2013) Common regulators of virulence in streptococci. Curr Top Microbiol Immunol 368, 111–153.
24. Hondorp ER and McIver KS (2007) The Mga virulence regulon: infection where the grass is greener. Mol Microbiol 66, 1056–1065.
25. McIver KS (2009) Stand-alone response regulators controlling global virulence networks in Streptococcus pyogenes. Contrib Microbiol 16, 103–119.
26. Miller EW, Cao TN, Pflughoeft KJ and Sumby P (2014) RNA-mediated regulation in Gram-positive pathogens: an overview punctuated with examples from the group A Streptococcus. Mol Microbiol 94, 9–20.
27. Hasty DL, Ofek I, Courtney HS and Doyle RJ (1992) Multiple adhesins of streptococci. Infect Immun 60, 2147–2152.
28. Edwards AM, Manetti AG, Falugi F, Zingaretti C, Capo S, Buccato S, Bensi G, Telford JL, Margarit I and Grandi G (2008) Scavenger receptor gp340 aggregates group A streptococci by binding pili. Mol Microbiol 68, 1378–1394.
29. Manetti AG, Zingaretti C, Falugi F, Capo S, Bombaci M, Bagnoli F, Gambellini G, Bensi G, Mora M, Edwards AM et al. (2007) Streptococcus pyogenes pili promote pharyngeal cell adhesion and biofilm formation. Mol Microbiol 64, 968–983.
30. Abbot EL, Smith WD, Siou GPS, Chiriboga C, Smith RJ, Wilson JA, Hirst BH and Kehoe MA (2007) Pili mediate specific adhesion of Streptococcus pyogenes to human tonsil and skin. Cell Microbiol 9, 1822–1833.
31. 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, 6172–6176.
32. Ozeri V, Tovi A, Burstein I, Natanson-Yaron S, Caparon MG, Yamada KM, Akiyama SK, Vlodavsky I and Hanski E (1996) A two-domain mechanism for group A streptococcal adherence through protein F to the extracellular matrix. EMBO J 15, 989–998.
33. Hanski E, Jaffe J and Ozeri V (1996) Proteins F1 and F2 of Streptococcus pyogenes. Properties of fibronectin binding. Adv Exp Med Biol 408, 141–150.
34. Walden M, Edwards JM, Dziewulska AM, Bergmann R, Saalbach G, Kan SY, Miller OK, Weckener M, Jackson RJ, Shirran SL et al. (2015) An internal thioester in a pathogen surface protein mediates covalent host binding. Elife 2, doi:10.7554/eLife.06638.
35. Katerov V, Andreev A, Schalen C and Totolian AA (1998) Protein F, a fibronectin-binding protein of Streptococcus pyogenes, also binds human fibrinogen: isolation of the protein and mapping of the binding region. Microbiology 144, 119–126.
36. Margarit I, Bonacci S, Pietrocola G, Rindi S, Ghezzo C, Bombaci M, Nardi-Dei V, Grifantini R, Speziale P and Grandi G (2009) Capturing host–pathogen interactions by protein microarrays: identification of novel streptococcal proteins binding to human fibronectin, fibrinogen, and C4BP. FASEB J 23, 3100–3112.
37. Jaffe J, Natanson-Yaron S, Caparon MG and Hanski E (1996) Protein F2, a novel fibronectin-binding protein from Streptococcus pyogenes, possesses two binding domains. Mol Microbiol 21, 373–384.
38. 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, 47428–47435.
39. Ramachandran V, McArthur JD, Behm CE, Gutzeit C, Dowton M, Fagan PK, Towers R, Currie B, Sriprakash KS and Walker MJ (2004) Two distinct genotypes of prtF2, encoding a fibronectin binding protein, and evolution of the gene family in Streptococcus pyogenes. J Bacteriol 186, 7601–7609.
40. Kreikemeyer B, Oehmcke S, Nakata M, Hoffrogge R and Podbielski A (2004) Streptococcus pyogenes fibronectin-binding protein F2: expression profile, binding characteristics, and impact on eukaryotic cell interactions. J Biol Chem 279, 15850–15859.
41. Kreikemeyer B, Nakata M, Oehmcke S, Gschwendtner C, Normann J and Podbielski A (2005) Streptococcus pyogenes collagen type I-binding Cpa surface protein. Expression profile, binding characteristics, biological functions, and potential clinical impact. J Biol Chem 280, 33228–33239.
42. Becherelli M, Manetti AG, Buccato S, Viciani E, Ciucchi L, Mollica G, Grandi G and Margarit I (2012) The ancillary protein 1 of Streptococcus pyogenes FCT-1 pili mediates cell adhesion and biofilm formation through heterophilic as well as homophilic interactions. Mol Microbiol 83, 1035–1047.
43. Linke-Winnebeck C, Paterson NG, Young PG, Middleditch MJ, Greenwood DR, Witte G and Baker EN (2014) Structural model for covalent adhesion of the Streptococcus pyogenes pilus through a thioester bond. J Biol Chem 289, 177–189.
44. Courtney HS, Li Y, Twal WO and Argraves WS (2009) Serum opacity factor is a streptococcal receptor for the extracellular matrix protein fibulin-1. J Biol Chem 284, 12966–12971.
45. Kreikemeyer B Talay SR and Chhatwal GS (1995) Characterization of a novel fibronectin-binding surface protein in group A streptococci. Mol Microbiol 17, 137–145.
46. Kreikemeyer B, Martin DR and Chhatwal GS (1999) SfbII protein, a fibronectin binding surface protein of group A streptococci, is a serum opacity factor with high serotype-specific apolipoproteinase activity. FEMS Microbiol Lett 178, 305–311.
47. Gillen CM, Courtney HS, Schulze K, Rohde M, Wilson MR, Timmer AM, Guzman CA, Nizet V, Chhatwal GS and Walker MJ (2008) Opacity factor activity and epithelial cell binding by the serum opacity factor protein of Streptococcus pyogenes are functionally discrete. J Biol Chem 283, 6359–6366.
48. 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, 1208–1217.
49. Oehmcke S, Podbielski A and Kreikemeyer B (2004) Function of the fibronectin-binding serum opacity factor of Streptococcus pyogenes in adherence to epithelial cells. Infect Immun 72, 4302–4308.
50. 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, 75–86.
51. Pandiripally V, Gregory E and Cue D (2002) Acquisition of regulators of complement activation by Streptococcus pyogenes serotype M1. Infect Immun 70, 6206–6214.
52. Terao Y, Okamoto S, Kataoka K, Hamada S and Kawabata S (2005) Protective immunity against Streptococcus pyogenes challenge in mice after immunization with fibronectin-binding protein. J Infect Dis 192, 2081–2091.
53. Oliver-Kozup H, Martin KH, Schwegler-Berry D, Green BJ, Betts C, Shinde AV, Van De Water L and Lukomski S (2013) The group A streptococcal collagen-like protein-1, Scl1, mediates biofilm formation by targeting the extra domain A-containing variant of cellular fibronectin expressed in wounded tissue. Mol Microbiol 87, 672–689.
54. Caswell CC, Oliver-Kozup H, Han R, Lukomska E and Lukomski S (2010) Scl1, the multifunctional adhesin of group A Streptococcus, selectively binds cellular fibronectin and laminin, and mediates pathogen internalization by human cells. FEMS Microbiol Lett 303, 61–68.
55. Chen S-M, Tsai Y-S, Wu C-M, Liao S-K, Wu L-C, Chang C-S, Liu Y-H and Tsai P-J (2010) Streptococcal collagen-like surface protein 1 promotes adhesion to the respiratory epithelial cell. BMC Microbiol 10, 320.
56. Humtsoe JO, Kim JK, Xu Y, Keene DR, Hook M, Lukomski S and Wary KK (2005) A streptococcal collagen-like protein interacts with the α2β1 integrin and induces intracellular signaling. J Biol Chem 280, 13848–13857.
57. Caswell CC, Barczyk M, Keene DR, Lukomska E, Gullberg DE and Lukomski S (2008) Identification of the first prokaryotic collagen sequence motif that mediates binding to human collagen receptors, integrins α2β1 and α11β1. J Biol Chem 283, 36168–36175.
58. Caswell CC, Lukomska E, Seo NS, Hook M and Lukomski S (2007) Scl1-dependent internalization of group A Streptococcus via direct interactions with the α2β1 integrin enhances pathogen survival and re-emergence. Mol Microbiol 64, 1319–1331.
59. Caswell CC, Han R, Hovis KM, Ciborowski P, Keene DR, Marconi RT and Lukomski S (2008) The Scl1 protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H, and inhibits the alternative pathway of complement. Mol Microbiol 67, 584–596.
60. Gao Y, Liang C, Zhao R, Lukomski S and Han R (2010) The Scl1 of M41-type group A Streptococcus binds the high-density lipoprotein. FEMS Microbiol Lett 309, 55–61.
61. Han R, Caswell CC, Lukomska E, Keene DR, Pawlowski M, Bujnicki JM, Kim JK and Lukomski S (2006) Binding of the low-density lipoprotein by streptococcal collagen-like protein Scl1 of Streptococcus pyogenes. Mol Microbiol 61, 351–367.
62. Reuter M, Caswell CC, Lukomski S and Zipfel PF (2010) Binding of the human complement regulators CFHR1 and factor H by streptococcal collagen-like protein 1 (Scl1) via their conserved C termini allows control of the complement cascade at multiple levels. J Biol Chem 285, 38473–38485.
63. Hryniewicz W, Lipinski B and Jeljaszewicz J (1972) Nature of the interaction between M protein of Streptococcus pyogenes and fibrinogen. J Infect Dis 125, 626–630.
64. Horstmann RD, Sievertsen HJ, Knobloch J and Fischetti VA (1988) Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci USA 85, 1657–1661.
65. Kotarsky H, Hellwage J, Johnsson E, Skerka C, Svensson HG, Lindahl G, Sjobring U and Zipfel PF (1998) Identification of a domain in human factor H and factor H-like protein-1 required for the interaction with streptococcal M proteins. J Immunol 160, 3349–3354.
66. Okada N, Liszewski MK, Atkinson JP 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, 2489–2493.
67. Bjorck L, Tylewska SK, Wadstrom T and Kronvall G (1981) Beta 2-microglobulin is bound to streptococcal M protein. Scand J Immunol 13, 391–394.
68. Schmidt KH, Mann K, Cooney J and Kohler W (1993) Multiple binding of type 3 streptococcal M protein to human fibrinogen, albumin and fibronectin. FEMS Immunol Med Microbiol 7, 135–143.
69. Ringdahl U and Sjobring U (2000) Analysis of plasminogen-binding M proteins of Streptococcus pyogenes. Methods 21, 143–150.
70. Ryan PA, Pancholi V and Fischetti VA (2001) Group A streptococci bind to mucin and human pharyngeal cells through sialic acid-containing receptors. Infect Immun 69, 7402–7412.
71. Giannakis E, Jokiranta TS, Ormsby RJ, Duthy TG, Male DA, Christiansen D, Fischetti VA, Bagley C, Loveland BE and Gordon DL (2002) Identification of the streptococcal M protein binding site on membrane cofactor protein (CD46). J Immunol 168, 4585–4592.
72. Dinkla K, Rohde M, Jansen WTM, Kaplan EL, Chhatwal GS and Talay SR (2003) Rheumatic fever–associated Streptococcus pyogenes isolates aggregate collagen. J Clin Invest 111, 1905–1912.
73. Carlsson F, Berggård K, Stålhammar-Carlemalm M and Lindahl G (2003) Evasion of phagocytosis through cooperation between two ligand-binding regions in Streptococcus pyogenes M protein. J Exp Med 198, 1057–1068.
74. Frick IM, Schmidtchen A and Sjobring U (2003) Interactions between M proteins of Streptococcus pyogenes and glycosaminoglycans promote bacterial adhesion to host cells. Eur J Biochem 270, 2303–2311.
75. Anderson EL, Cole JN, Olson J, Ryba B, Ghosh P and Nizet V (2014) The fibrinogen-binding M1 protein reduces pharyngeal cell adherence and colonization phenotypes of M1T1 group A Streptococcus. J Biol Chem 289, 3539–3546.
76. Bober M, Morgelin M, Olin AI, von Pawel-Rammingen U and Collin M (2011) The membrane bound LRR lipoprotein Slr, and the cell wall-anchored M1 protein from Streptococcus pyogenes both interact with type I collagen. PLoS One 6, e20345.
77. Stenberg L, O'Toole P and Lindahl G (1992) Many group A streptococcal strains express two different immunoglobulin-binding proteins, encoded by closely linked genes: characterization of the proteins expressed by four strains of different M-type. Mol Microbiol 6, 1185–1194.
78. Johnsson E, Andersson G, Lindahl G and Heden LO (1994) Identification of the IgA-binding region in streptococcal protein Arp. J Immunol 153, 3557–3564.
79. Lindahl G and Akerstrom B (1989) Receptor for IgA in group A streptococci: cloning of the gene and characterization of the protein expressed in Escherichia coli. Mol Microbiol 3, 239–247.
80. Stenberg L, O'Toole P, Mestecky J and Lindahl G (1994) Molecular characterization of protein Sir, a streptococcal cell surface protein that binds both immunoglobulin A and immunoglobulin G. J Biol Chem 269, 13458–13464.
81. Elsner A, Kreikemeyer B, Braun-Kiewnick A, Spellerberg B, Buttaro BA 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, 4859–4869.
82. 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, 993–997.
83. Wistedt AC, Ringdahl U, Muller-Esterl W and Sjobring U (1995) Identification of a plasminogen-binding motif in PAM, a bacterial surface protein. Mol Microbiol 18, 569–578.
84. Sanderson-Smith ML, Dowton M, Ranson M and Walker MJ (2007) The plasminogen-binding group A streptococcal M protein-related protein Prp binds plasminogen via arginine and histidine residues. J Bacteriol 189, 1435–1440.
85. Linke C, Siemens N, Oehmcke S, Radjainia M, Law RHP, Whisstock JC, Baker EN and Kreikemeyer B (2012) The extracellular protein factor Epf from Streptococcus pyogenes is a cell surface adhesin that binds to cells through an N-terminal domain containing a carbohydrate-binding module. J Biol Chem 287, 38178–38189.
86. Zhang S, Green NM, Sitkiewicz I, Lefebvre RB and Musser JM (2006) Identification and characterization of an antigen I/II family protein produced by group A Streptococcus. Infect Immun 74, 4200–4213.
87. Maddocks SE, Wright CJ, Nobbs AH, Brittan JL, Franklin L, Strömberg N, Kadioglu A, Jepson MA and Jenkinson HF (2011) Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential ligand-binding properties and mediates biofilm formation. Mol Microbiol 81, 1034–1049.
88. Franklin L, Nobbs AH, Bricio-Moreno L, Wright CJ, Maddocks SE, Sahota JS, Ralph J, O'Connor M, Jenkinson HF and Kadioglu A (2013) The AgI/II family adhesin AspA is required for respiratory infection by Streptococcus pyogenes. PLoS One 8, e62433.
89. Murakami J, Terao Y, Morisaki I, Hamada S and Kawabata S (2012) Group A Streptococcus adheres to pharyngeal epithelial cells with salivary proline-rich proteins via GrpE chaperone protein. J Biol Chem 287, 22266–22275.
90. Akesson P, Cooney J, Kishimoto F and Bjorck L (1990) Protein H –a novel IgG binding bacterial protein. Mol Immunol 27, 523–531.
91. Frick IM, Akesson P, Cooney J, Sjobring U, Schmidt KH, Gomi H, Hattori S, Tagawa C, Kishimoto F and Bjorck L (1994) Protein H –a surface protein of Streptococcus pyogenes with separate binding sites for IgG and albumin. Mol Microbiol 12, 143–151.
92. Hytönen J, Haataja S and Finne J (2003) Streptococcus pyogenes glycoprotein-binding strepadhesin activity is mediated by a surface-associated carbohydrate-degrading enzyme, pullulanase. Infect Immun 71, 784–793.
93. Stalhammar-Carlemalm M, Areschoug T, Larsson C and Lindahl G (1999) The R28 protein of Streptococcus pyogenes is related to several group B streptococcal surface proteins, confers protective immunity and promotes binding to human epithelial cells. Mol Microbiol 33, 208–219.
94. Bensi G, Mora M, Tuscano G, Biagini M, Chiarot E, Bombaci M, Capo S, Falugi F, Manetti AGO, Donato P et al. (2012) Multi high-throughput approach for highly selective identification of vaccine candidates: the group A Streptococcus case. Mol Cell Proteomics 11, M111.015693.
95. Gallotta M, Gancitano G, Pietrocola G, Mora M, Pezzicoli A, Tuscano G, Chiarot E, Nardi-Dei V, Taddei AR, Rindi S et al. (2014) SpyAD, a moonlighting protein of group A Streptococcus contributing to bacterial division and host cell adhesion. Infect Immun 82, 2890–2901.
96. Schneewind O, Mihaylova-Petkov D and Model P (1993) Cell wall sorting signals in surface proteins of gram-positive bacteria. EMBO J 12, 4803–4811.
97. Barnett TC and Scott JR (2002) Differential recognition of surface proteins in Streptococcus pyogenes by two sortase gene homologs. J Bacteriol 184, 2181–2191.
98. Scott JR and Barnett TC (2006) Surface proteins of gram-positive bacteria and how they get there. Annu Rev Microbiol 60, 397–423.
99. Barnett TC, Patel AR and Scott JR (2004) A novel sortase, SrtC2, from Streptococcus pyogenes anchors a surface protein containing a QVPTGV motif to the cell wall. J Bacteriol 186, 5865–5875.
100. Mora M, Bensi G, Capo S, Falugi F, Zingaretti C, Manetti AG, Maggi T, Taddei AR, Grandi G and Telford JL (2005) Group A Streptococcus produce pilus-like structures containing protective antigens and Lancefield T antigens. Proc Natl Acad Sci USA 102, 15641–15646.
101. Hendrickx AP, Budzik JM, Oh SY and Schneewind O (2011) Architects at the bacterial surface –sortases and the assembly of pili with isopeptide bonds. Nat Rev Microbiol 9, 166–176.
102. Schneewind O and Missiakas D (2014) Sec-secretion and sortase-mediated anchoring of proteins in Gram-positive bacteria. Biochim Biophys Acta 1843, 1687–1697.
103. Spirig T, Weiner EM and Clubb RT (2011) Sortase enzymes in Gram-positive bacteria. Mol Microbiol 82, 1044–1059.
104. Falugi F, Zingaretti C, Pinto V, Mariani M, Amodeo L, Manetti AG, Capo S, Musser JM, Orefici G, Margarit I et al. (2008) Sequence variation in group A Streptococcus pili and association of pilus backbone types with lancefield T serotypes. J Infect Dis 198, 1834–1841.
105. Kang HJ, Coulibaly F, Proft T and Baker EN (2011) Crystal structure of Spy0129, a Streptococcus pyogenes class B sortase involved in pilus assembly. PLoS One 6, e15969.
106. Quigley BR, Zahner D, Hatkoff M, Thanassi DG and Scott JR (2009) Linkage of T3 and Cpa pilins in the Streptococcus pyogenes M3 pilus. Mol Microbiol 72, 1379–1394.
107. Smith WD, Pointon JA, Abbot E, Kang HJ, Baker EN, Hirst BH, Wilson JA, Banfield MJ and Kehoe MA (2010) Roles of minor pilin subunits Spy0125 and Spy0130 in the serotype M1 Streptococcus pyogenes strain SF370. J Bacteriol 192, 4651–4659.
108. Nakata M, Kimura KR, Sumitomo T, Wada S, Sugauchi A, Oiki E, Higashino M, Kreikemeyer B, Podbielski A, Okahashi N et al. (2011) Assembly mechanism of FCT region type 1 pili in serotype M6 Streptococcus pyogenes. J Biol Chem 286, 37566–37577.
109. Danne C and Dramsi S (2012) Pili of gram-positive bacteria: roles in host colonization. Res Microbiol 163, 645–658.
110. Kreikemeyer B, Gámez G, Margarit I, Giard J-C, Hammerschmidt S, Hartke A and Podbielski A (2011) Genomic organization, structure, regulation and pathogenic role of pilus constituents in major pathogenic streptococci and enterococci. Int J Med Microbiol 301, 240–251.
111. Ton-That H and Schneewind O (2004) Assembly of pili in Gram-positive bacteria. Trends Microbiol 12, 228–234.
112. Bessen DE and Kalia A (2002) Genomic localization of a T serotype locus to a recombinatorial zone encoding extracellular matrix-binding proteins in Streptococcus pyogenes. Infect Immun 70, 1159–1167.
113. Kratovac Z, Manoharan A, Luo F, Lizano S and Bessen DE (2007) Population genetics and linkage analysis of loci within the FCT region of Streptococcus pyogenes. J Bacteriol 189, 1299–1310.
114. Köller T, Manetti AGO, Kreikemeyer B, Lembke C, Margarit I, Grandi G and Podbielski A (2010) Typing of the pilus-protein-encoding FCT region and biofilm formation as novel parameters in epidemiological investigations of Streptococcus pyogenes isolates from various infection sites. J Med Microbiol 59, 442–452.
115. Crotty Alexander LE, Maisey HC, Timmer AM, Rooijakkers SH, Gallo RL, von Kockritz-Blickwede M and Nizet V (2010) M1T1 group A streptococcal pili promote epithelial colonization but diminish systemic virulence through neutrophil extracellular entrapment. J Mol Med 88, 371–381.
116. Kimura KR, Nakata M, Sumitomo T, Kreikemeyer B, Podbielski A, Terao Y and Kawabata S (2012) Involvement of T6 pili in biofilm formation by serotype M6 Streptococcus pyogenes. J Bacteriol 194, 804–812.
117. Nakata M, Koller T, Moritz K, Ribardo D, Jonas L, McIver KS, Sumitomo T, Terao Y, Kawabata S, Podbielski A et al. (2009) Mode of expression and functional characterization of FCT-3 pilus region-encoded proteins in Streptococcus pyogenes serotype M49. Infect Immun 77, 32–44.
118. Lizano S, Luo F and Bessen DE (2007) Role of streptococcal T antigens in superficial skin infection. J Bacteriol 189, 1426–1434.
119. Patti JM, Allen BL, McGavin MJ and Hook M (1994) MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol 48, 585–617.
120. Hytönen 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, 512–519.
121. Stockbauer KE, Magoun L, Liu M, Burns EH, Gubba S, Renish S, Pan X, Bodary SC, Baker E, Coburn J et al. (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 α5β3 and α2bβ3. Proc Natl Acad Sci USA 96, 242–247.
122. Tsai WH, Chang CW, Lin YS, Chuang WJ, Wu JJ, Liu CC, Tsai PJ and Lin MT (2008) Streptococcal pyrogenic exotoxin B-induced apoptosis in A549 cells is mediated through α5β3 integrin and Fas. Infect Immun 76, 1349–1357.
123. Sitkiewicz I, Nagiec MJ, Sumby P, Butler SD, Cywes-Bentley C and Musser JM (2006) Emergence of a bacterial clone with enhanced virulence by acquisition of a phage encoding a secreted phospholipase A2. Proc Natl Acad Sci USA 103, 16009–16014.
124. Olsen RJ, Shelburne SA and Musser JM (2009) Molecular mechanisms underlying group A streptococcal pathogenesis. Cell Microbiol 11, 1–12.
125. Fisher M, Huang Y-S, Li X, McIver KS, Toukoki C and Eichenbaum Z (2008) Shr is a broad-spectrum surface receptor that contributes to adherence and virulence in group A Streptococcus. Infect Immun 76, 5006–5015.
126. Bates CS, Montañez GE, Woods CR, Vincent RM and Eichenbaum Z (2003) Identification and characterization of a Streptococcus pyogenes operon involved in binding of hemoproteins and acquisition of iron. Infect Immun 71, 1042–1055.
127. Lu C, Xie G, Liu M, Zhu H and Lei B (2012) Direct heme transfer reactions in the group A Streptococcus heme acquisition pathway. PLoS One 7, e37556.
128. Pancholi V and Fischetti VA (1992) A major surface protein on group A streptococci is a glyceraldehyde-3-phosphate-dehydrogenase with multiple binding activity. J Exp Med 176, 415–426.
129. Winram SB and Lottenberg R (1996) The plasmin-binding protein Plr of group A streptococci is identified as glyceraldehyde-3-phosphate dehydrogenase. Microbiology 142, 2311–2320.
130. Jin H, Song YP, Boel G, Kochar J and Pancholi V (2005) Group A streptococcal surface GAPDH, SDH, recognizes uPAR/CD87 as its receptor on the human pharyngeal cell and mediates bacterial adherence to host cells. J Mol Biol 350, 27–41.
131. Jin H, Agarwal S, Agarwal S & Pancholi V (2011) Surface export of GAPDH/SDH, a glycolytic enzyme, is essential for Streptococcus pyogenes virulence.mBio 2, e00068-11.
132. Boël G, Jin H and Pancholi V (2005) Inhibition of cell surface export of group A streptococcal anchorless surface dehydrogenase affects bacterial adherence and antiphagocytic properties. Infect Immun 73, 6237–6248.
133. Winram SB and Lottenberg R (1998) Site-directed mutagenesis of streptococcal plasmin receptor protein (Plr) identifies the C-terminal Lys334 as essential for plasmin binding, but mutation of the plr gene does not reduce plasmin binding to group A streptococci. Microbiology 144, 2025–2035.
134. Pancholi V and Fischetti VA (1998) α-Enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci. J Biol Chem 273, 14503–14515.
135. Derbise A, Song YP, Parikh S, Fischetti VA and Pancholi V (2004) Role of the C-terminal lysine residues of streptococcal surface enolase in glu- and lys-plasminogen-binding activities of group A streptococci. Infect Immun 72, 94–105.
136. Cork AJ, Jergic S, Hammerschmidt S, Kobe B, Pancholi V, Benesch JLP, Robinson CV, Dixon NE, Aquilina JA and Walker MJ (2009) Defining the structural basis of human plasminogen binding by streptococcal surface enolase. J Biol Chem 284, 17129–17137.
137. Courtney HS, Dale JB and Hasty DI (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, 2415–2419.
138. Courtney HS, Bronze MS, Dale JB and Hasty DL (1994) Analysis of the role of M24 protein in group A streptococcal adhesion and colonization by use of omega-interposon mutagenesis. Infect Immun 62, 4868–4873.
139. Yamaguchi M, Terao Y and Kawabata S (2013) Pleiotropic virulence factor –Streptococcus pyogenes fibronectin-binding proteins. Cell Microbiol 15, 503–511.
140. Hanski E, Horwitz PA and Caparon MG (1992) Expression of protein F, the fibronectin-binding protein of Streptococcus pyogenes JRS4, in heterologous streptococcal and enterococcal strains promotes their adherence to respiratory epithelial cells. Infect Immun 60, 5119–5125.
141. Talay SR, Valentin-Weigand P, Jerlstrom PG, Timmis KN and Chhatwal GS (1992) Fibronectin-binding protein of Streptococcus pyogenes: sequence of the binding domain involved in adherence of streptococci to epithelial cells. Infect Immun 60, 3837–3844.
142. Timmer AM, Kristian SA, Datta V, Jeng A, Gillen CM, Walker MJ, Beall B and Nizet V (2006) Serum opacity factor promotes group A streptococcal epithelial cell invasion and virulence. Mol Microbiol 62, 15–25.
143. Dahesh S, Nizet V and Cole JN (2012) Study of streptococcal hemoprotein receptor (Shr) in iron acquisition and virulence of M1T1 group A Streptococcus. Virulence 3, 566–575.
144. Amelung S, Nerlich A, Rohde M, Spellerberg B, Cole JN, Nizet V, Chhatwal GS and Talay SR (2011) The FbaB-type fibronectin-binding protein of Streptococcus pyogenes promotes specific invasion into endothelial cells. Cell Microbiol 13, 1200–1211.
145. Okada N, Tatsuno I, Hanski E, Caparon M and Sasakawa C (1998) Streptococcus pyogenes protein F promotes invasion of HeLa cells. Microbiology 144, 3079–3086.
146. Rezcallah MS, Hodges K, Gill DB, Atkinson JP, Wang B and Cleary PP (2005) Engagement of CD46 and α5β1 integrin by group A streptococci is required for efficient invasion of epithelial cells. Cell Microbiol 7, 645–653.
147. Courtney HS, Dale JB and Hasty DL (2002) Mapping the fibrinogen-binding domain of serum opacity factor of group a streptococci. Curr Microbiol 44, 236–240.
148. Hong K (2007) Characterization of group a streptococcal M23 protein and comparison of the M3 and M23 protein's ligand-binding domains. Curr Microbiol 55, 427–434.
149. Dinkla K, Rohde M, Jansen WT, Carapetis JR, Chhatwal GS and Talay SR (2003) Streptococcus pyogenes recruits collagen via surface-bound fibronectin: a novel colonization and immune evasion mechanism. Mol Microbiol 47, 861–869.
150. Hyland KA, Wang B and Cleary PP (2007) Protein F1 and Streptococcus pyogenes resistance to phagocytosis. Infect Immun 75, 3188–3191.
151. Bober M, Enochsson C, Collin M and Morgelin M (2010) Collagen VI is a subepithelial adhesive target for human respiratory tract pathogens. J Innate Immun 2, 160–166.
152. Linke C, Caradoc-Davies TT, Young PG, Proft T and Baker EN (2009) The laminin-binding protein Lbp from Streptococcus pyogenes is a zinc receptor. J Bacteriol 191, 5814–5823.
153. Xu Y, Keene DR, Bujnicki JM, Hook M and Lukomski S (2002) Streptococcal Scl1 and Scl2 proteins form collagen-like triple helices. J Biol Chem 277, 27312–27318.
154. Lukomski S, Nakashima K, Abdi I, Cipriano VJ, Ireland RM, Reid SD, Adams GG and Musser JM (2000) Identification and characterization of the scl gene encoding a group A Streptococcus extracellular protein virulence factor with similarity to human collagen. Infect Immun 68, 6542–6553.
155. Phillips GN Jr, Flicker PF, Cohen C, Manjula BN and Fischetti VA (1981) Streptococcal M protein: alpha-helical coiled-coil structure and arrangement on the cell surface. Proc Natl Acad Sci USA 78, 4689–4693.
156. Fischetti VA, Pancholi V and Schneewind O (1990) Conservation of a hexapeptide sequence in the anchor region of surface proteins from gram-positive cocci. Mol Microbiol 4, 1603–1605.
157. Smeesters PR, McMillan DJ and Sriprakash KS (2010) The streptococcal M protein: a highly versatile molecule. Trends Microbiol 18, 275–282.
158. Fischetti VA (2016) M protein and other surface proteins on streptococci. In Streptococcus pyogenes: Basic Biology to Clinical Manifestations (Ferretti JJ, Stevens DL and Fischetti VA, eds), pp. 23–43. University of Oklahoma Health Sciences Center, Oklahoma City, OK.
159. Sanderson-Smith M, De Oliveira DM, Guglielmini J, McMillan DJ, Vu T, Holien JK, Henningham A, Steer AC, Bessen DE, Dale JB et al. (2014) A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development. J Infect Dis 210, 1325–1338.
160. McArthur JD and Walker MJ (2006) Domains of group A streptococcal M protein that confer resistance to phagocytosis, opsonization and protection: implications for vaccine development. Mol Microbiol 59, 1–4.
161. Berkower C, Ravins M, Moses AE 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, 1463–1475.
162. Courtney HS, Liu S, Dale JB and Hasty DL (1997) 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, 2472–2474.
163. Courtney HS, Ofek I and Hasty DL (1997) 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, 65–70.
164. Cue D, Dombek PE, Lam H and Cleary PP (1998) Streptococcus pyogenes serotype M1 encodes multiple pathways for entry into human epithelial cells. Infect Immun 66, 4593–4601.
165. Feito MJ, Sanchez A, Oliver MA, Perez-Caballero D, Rodriguez de Cordoba S, Alberti S and Rojo JM (2007) Membrane cofactor protein (MCP, CD46) binding to clinical isolates of Streptococcus pyogenes: binding to M type 18 strains is independent of Emm or Enn proteins. Mol Immunol 44, 3571–3579.
166. Caparon MG, Stephens DS, Olsen A and Scott JR (1991) Role of M protein in adherence of group A streptococci. Infect Immun 59, 1811–1817.
167. Hauser AR and Schlievert PM (1990) Nucleotide sequence of the streptococcal pyrogenic exotoxin type B gene and relationship between the toxin and the streptococcal proteinase precursor. J Bacteriol 172, 4536–4542.
168. Chiang-Ni C and Wu J-J (2008) Effects of streptococcal pyrogenic exotoxin B on pathogenesis of Streptococcus pyogenes. J Formos Med Assoc 107, 677–685.
169. Ruoslahti E (1996) RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol 12, 697–715.
170. Ishibashi Y, Relman DA and Nishikawa A (2001) Invasion of human respiratory epithelial cells by Bordetella pertussis: possible role for a filamentous hemagglutinin Arg-Gly-Asp sequence and α5β1 integrin. Microb Pathog 30, 279–288.
171. Eto DS, Jones TA, Sundsbak JL and Mulvey MA (2007) Integrin-mediated host cell invasion by type 1-piliated uropathogenict Escherichia coli. PLoS Pathog 3, e100.
172. Cole JN, Barnett TC, Nizet V and Walker MJ (2011) Molecular insight into invasive group A streptococcal disease. Nat Rev Microbiol 9, 724–736.
173. Tsai PJ, Kuo CF, Lin KY, Lin YS, Lei HY, Chen FF, Wang JR and Wu JJ (1998) Effect of group A streptococcal cysteine protease on invasion of epithelial cells. Infect Immun 66, 1460–1466.
174. Burns EH Jr, Lukomski S, Rurangirwa J, Podbielski A and Musser JM (1998) Genetic inactivation of the extracellular cysteine protease enhances in vitro internalization of group A streptococci by human epithelial and endothelial cells. Microb Pathog 24, 333–339.
175. 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, 462–469.
176. Chaussee MS, Cole RL and van Putten JP (2000) Streptococcal erythrogenic toxin B abrogates fibronectin-dependent internalization of Streptococcus pyogenes by cultured mammalian cells. Infect Immun 68, 3226–3232.
177. Beres SB, Sylva GL, Barbian KD, Lei B, Hoff JS, Mammarella ND, Liu MY, Smoot JC, Porcella SF, Parkins LD et al. (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, 10078–10083.
178. Nagiec MJ, Lei B, Parker SK, Vasil ML, Matsumoto M, Ireland RM, Beres SB, Hoe NP and Musser JM (2004) Analysis of a novel prophage-encoded group A Streptococcus extracellular phospholipase A2. J Biol Chem 279, 45909–45918.
179. Shelburne SA, Granville C, Tokuyama M, Sitkiewicz I, Patel P and Musser JM (2005) Growth characteristics of and virulence factor production by group A Streptococcus during cultivation in human saliva. Infect Immun 73, 4723–4731.
180. Zhu H, Liu M and Lei B (2008) The surface protein Shr of Streptococcus pyogenes binds heme and transfers it to the streptococcal heme-binding protein Shp. BMC Microbiol 8, 15.
181. Pancholi V and Chhatwal GS (2003) Housekeeping enzymes as virulence factors for pathogens. Int J Med Microbiol 293, 391–401.
182. Lottenberg R, Broder CC, Boyle MDP, Kain SJ, Schroeder BL and Curtiss Iii R (1992) Cloning, sequence analysis, and expression in Escherichia coli of a streptococcal plasmin receptor. J Bacteriol 174, 5204–5210.
183. Pancholi V and Fischetti VA (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, 1633–1643.
184. Karbassi F, Quiros V, Pancholi V and Kornblatt MJ (2010) Dissociation of the octameric enolase from S. pyogenes –one interface stabilizes another. PLoS One 5, e8810.
185. Sumitomo T, Nakata M, Higashino M, Yamaguchi M and Kawabata S (2016) Group A Streptococcus exploits human plasminogen for bacterial translocation across epithelial barrier via tricellular tight junctions. Sci Rep 7, 20069.
186. Courtney HS, Li Y, Dale JB and Hasty DL (1994) Cloning, sequencing, and expression of a fibronectin/fibrinogen-binding protein from group A streptococci. Infect Immun 62, 3937–3946.
187. Lembke C, Podbielski A, Hidalgo-Grass C, Jonas L, Hanski E and Kreikemeyer B (2006) Characterization of biofilm formation by clinically relevant serotypes of group A streptococci. Appl Environ Microbiol 72, 2864–2875.
188. Thenmozhi R, Balaji K, Kumar R, Rao TS and Pandian SK (2011) Characterization of biofilms in different clinical M serotypes of Streptococcus pyogenes. J Basic Microbiol 51, 196–204.
189. Conley J, Olson ME, Cook LS, Ceri H, Phan V and Davies HD (2003) Biofilm formation by Group A streptococci: is there a relationship with treatment failure? J Clin Microbiol 41, 4043–4048.
190. Manetti AGO, Köller T, Becherelli M, Buccato S, Kreikemeyer B, Podbielski A, Grandi G and Margarit I (2010) Environmental acidification drives S. pyogenes pilus expression and microcolony formation on epithelial cells in a FCT-dependent manner. PLoS One 5, e13864.
191. Doern CD, Roberts AL, Hong W, Nelson J, Lukomski S, Swords WE and Reid SD (2009) Biofilm formation by group A Streptococcus: a role for the streptococcal regulator of virulence (Srv) and streptococcal cysteine protease (SpeB). Microbiology 155, 46–52.
192. Cho KH and Caparon MG (2005) Patterns of virulence gene expression differ between biofilm and tissue communities of Streptococcus pyogenes. Mol Microbiol 57, 1545–1556.
193. Marks LR, Mashburn-Warren L, Federle MJ and Hakansson AP (2014) Streptococcus pyogenes biofilm growth in vitro and in vivo and its role in colonization, virulence, and genetic exchange. J Infect Dis 210, 25–34.
194. Fiedler T, Riani C, Koczan D, Standar K, Kreikemeyer B and Podbielski A (2013) Protective mechanisms of respiratory tract streptococci against Streptococcus pyogenes biofilm formation and epithelial cell infection. Appl Environ Microbiol 79, 1265–1276.
195. Takemura N, Noiri Y, Ehara A, Kawahara T, Noguchi N and Ebisu S (2004) Single species biofilm-forming ability of root canal isolates on gutta-percha points. Eur J Oral Sci 112, 523–529.
196. Torretta S, Marchisio P, Drago L, Baggi E, De Vecchi E, Garavello W, Nazzari E, Pignataro L and Esposito S (2012) Nasopharyngeal biofilm-producing otopathogens in children with nonsevere recurrent acute otitis media. Otolaryngol Head Neck Surg 146, 991–996.
197. Hollands A, Pence MA, Timmer AM, Osvath SR, Turnbull L, Whitchurch CB, Walker MJ and Nizet V (2010) Genetic switch to hypervirulence reduces colonization phenotypes of the globally disseminated group A Streptococcus M1T1 clone. J Infect Dis 202, 11–19.
198. Parashar V, Aggarwal C, Federle MJ and Neiditch MB (2015) Rgg protein structure-function and inhibition by cyclic peptide compounds. Proc Natl Acad Sci USA 112, 5177–5182.
199. Cook LC and Federle MJ (2014) Peptide pheromone signaling in Streptococcus and Enterococcus. FEMS Microbiol Rev 38, 473–492.
200. Chang JC, LaSarre B, Jimenez JC, Aggarwal C and Federle MJ (2011) Two group A streptococcal peptide pheromones act through opposing Rgg regulators to control biofilm development. PLoS Pathog 7, e1002190.
201. Zutkis AA, Anbalagan S, Chaussee MS and Dmitriev AV (2014) Inactivation of the Rgg2 transcriptional regulator ablates the virulence of Streptococcus pyogenes. PLoS One 9, e114784.
202. Chang JC, Jimenez JC and Federle MJ (2015) Induction of a quorum sensing pathway by environmental signals enhances group A streptococcal resistance to lysozyme. Mol Microbiol 97, 1097–1113.
203. Fleuchot B, Guillot A, Mézange C, Besset C, Chambellon E, Monnet V and Gardan R (2013) Rgg-associated SHP signaling peptides mediate cross-talk in streptococci. PLoS One 8, e66042.
204. Cook LC, LaSarre B & Federle MJ (2013)Interspecies communication among commensal and pathogenic streptococci.mBio 4, e00382-13.
205. Wilkening RV, Chang JC and Federle MJ (2016) PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum sensing. Mol Microbiol 99, 71–87.
206. Makthal N, Gavagan M, Do H, Olsen RJ, Musser JM and Kumaraswami M (2016) Structural and functional analysis of RopB: a major virulence regulator in Streptococcus pyogenes. Mol Microbiol 99, 1119–1133.
207. Ma Y, Bryant AE, Salmi DB, McIndoo E and Stevens DL (2009) vfr, a novel locus affecting cysteine protease production in Streptococcus pyogenes. J Bacteriol 191, 3189–3194.
208. Shelburne SA, Olsen RJ, Makthal N, Brown NG, Sahasrabhojane P, Watkins EM, Palzkill T, Musser JM and Kumaraswami M (2011) An amino-terminal signal peptide of Vfr protein negatively influences RopB-dependent SpeB expression and attenuates virulence in Streptococcus pyogenes. Mol Microbiol 82, 1481–1495.
209. Connolly KL, Roberts AL, Holder RC and Reid SD (2011) Dispersal of group A streptococcal biofilms by the cysteine protease SpeB leads to increased disease severity in a murine model. PLoS One 6, e18984.
210. Loughman JA and Caparon MG (2006) A novel adaptation of aldolase regulates virulence in Streptococcus pyogenes. EMBO J 25, 5414–5422.