化膿性鏈球菌為人類重要的病原菌，所造成的感染與毒力因子之表現息息相關，且毒力因子的表現受到嚴密地調控。本實驗室先前的研究認為 Rgg 可整合外界訊號並啟動下游主要毒力因子 SpeB 的表現，然而至今對 Rgg 調控機轉的認識仍有限。DNA microarray 或蛋白質體學分析中認為受到 Rgg 影響的基因功能多元，且缺乏特定的結合序列，因此認為 Rgg 透過與其他分子結合，調控不同的基因表現，反應各種外界訊號。本研究主要在找尋與 Rgg 結合的蛋白質，利用rgg 突變株表現Rgg-TAP 蛋白，透過兩階段親和性標籤純化出可能與Rgg 結合之蛋白質。其中一蛋白質經由身份鑑定為噬菌體蛋白質Phi (phiNIH1.1_16)，並進一步以pull-down assay 證實Phi 與 Rgg 可互相結合。由於 phi 序列在噬菌體基因體位於高度變異區，依其鄰近基因特性，預測Phi 可能參與DNA 複製。本研究以real-time PCR 證實phi 突變株於mitomycin C刺激下確實減少噬菌體DNA 複製，同樣在rgg 突變株亦發現噬菌體 DNA 複製量下降，顯示兩者皆可正向控制噬菌體誘導。另外RT-PCR 分析發現Rgg 可正向調控phi 的轉錄，而phi 突變株則不影響 rgg mRNA 、speB mRNA 或蛋白質表現。這些研究結果顯示 Rgg 及Phi 皆可正向調控噬菌體複製，且 Rgg 可與Phi 進行蛋白質交互作用並調控phi 的表現。在近代對emm 1、emm 3 菌株之演化研究中，含有phi 的噬菌體扮演重要的角色，也暗示細菌受到環境壓力時，可能透過 Rgg 與Phi 的作調控路徑，增加宿主與噬菌體對環境壓力的適應能力，並促進化膿性鏈球菌的演化。

Streptococcus pyogenes (group A streptococcus, GAS), one of the major human pathogens, causes wide spectrum of diseases. The expression of virulence genes in GAS is controlled mainly by the interactions of transcriptional regulators. Previous studies in our lab suggested that Rgg, a global regulator, can coordinate environmental signals to turn on streptococcal pyogenic exotoxin B (SpeB) expression. However how Rgg to regulate gene expression is poorly understood. The absence of a conserved regulatory motif in the promoter region of Rgg-regulated genes and the
functional diversity of those associated gene products suggest that Rgg interacts with additional molecules. The aim of my project was trying to identify Rgg-interacted proteins and characterized the regulatory network. The rgg isogenic mutant was constructed and complemented with TAP-tagged Rgg. After tandem affinity purification, Rgg interacted protein candidates were found, and LC MS/MS analysis identified one protein as a phage encoded hypothetical protein, Phi. Physical interaction between Rgg and Phi was futher demonstrated by the pull-down assay. According to the location on phage genome, phi was predicted to be involved in phage DNA replication. Real-time PCR showed after mitomycin C treatment, mutants
defect in phi or rgg exhibited diminished prophage induction. RT-PCR showed no effect of the phi mutant on the rgg transcription or SpeB expression whereas Rgg positively regulate phi expression. These results suggest Rgg contributes to prophage induction through protein interaction and transcriptional regulation of phi. Epidemiology studies demonstrated emm1 and emm3 GAS acquired phi-containing phages had since gained widespread acceptance. Taken together, these findings provide crucial insight into the way that Rgg functions in prophage induction, and the molecular processes underlying evolution.

Akesson, P., A. G. Sjoholm, and L. Bjorck. Protein SIC, a novel extracellular protein of Streptococcus pyogenes interfering with complement function. J Biol Chem 271:1081-8. 1996.
Almengor, A. C., T. L. Kinkel, S. J. Day, and K. S. McIver. The Catabolite Control Protein CcpA binds to Pmga and influences expression of the virulence regulator Mga in the group A streptococcus. J Bacteriol 189:8405-8416. 2007.
Aziz, R. K., R. A. Edwards, W. W. Taylor, D. E. Low, A. McGeer, and M. Kotb. Mosaic prophages with horizontally acquired genes account for the emergence and diversification of the globally disseminated M1T1 clone of Streptococcus pyogenes. J Bacteriol 187:3311-8. 2005.
Aziz, R. K., and M. Kotb. Rise and persistence of global M1T1 clone of Streptococcus pyogenes. Emerg Infect Dis 14:1511-7. 2008.
Beres, S. B., and J. M. Musser. Contribution of exogenous genetic elements to the group A streptococcus metagenome. PLoS One 2:e800. 2007.
Beres, S. B., G. L. Sylva, K. D. Barbian, B. Lei, J. S. Hoff, N. D. Mammarella, M. Y. Liu, J. C. Smoot, S. F. Porcella, L. D. Parkins, D. S. Campbell, T. M. Smith, J. K. McCormick, D. Y. Leung, P. M. Schlievert, and J. M. Musser. 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 U S A 99:10078-83. 2002.
Binks, M. J., B. A. Fernie-King, D. J. Seilly, P. J. Lachmann, and K. S. Sriprakash. Attribution of the various inhibitory actions of the streptococcal inhibitor of complement (SIC) to regions within the molecule. J Biol Chem 280:20120-5. 2005.
Brenciani, A., A. Bacciaglia, C. Vignaroli, A. Pugnaloni, P. E. Varaldo, and E. Giovanetti. {Phi}m46.1, the Main Streptococcus pyogenes element carrying mef(A) and tet(O) genes. Antimicrob Agents Chemother 54:221-9. 2010.
Broudy, T. B., V. Pancholi, and V. A. Fischetti. The in vitro interaction of Streptococcus pyogenes with human pharyngeal cells induces a phage-encoded extracellular DNase. Infect Immun 70:2805-11. 2002.
Broudy, T. B., V. Pancholi, and V. A. Fischetti. Induction of lysogenic bacteriophage and phage-associated toxin from group A streptococci during coculture with human pharyngeal cells. Infect Immun 69:1440-3. 2001.
Caparon, M. G., R. T. Geist, J. Perez-Casal, and J. R. Scott. Environmental regulation of virulence in group A streptococci: transcription of the gene encoding M protein is stimulated by carbon dioxide. J. Bacteriol. 174:5693-701. 1992.
Carapetis, J. R., A. C. Steer, E. K. Mulholland, and M. Weber. The global burden of group A streptococcal diseases. Lancet Infect Dis 5:685-94. 2005.
Chatellier, S., N. Ihendyane, R. G. Kansal, F. Khambaty, H. Basma, A. Norrby-Teglund, D. E. Low, A. McGeer, and M. Kotb. Genetic relatedness and superantigen expression in group A streptococcus serotype M1 isolates from patients with severe and nonsevere invasive diseases. Infect Immun 68:3523-34. 2000.
Chaussee, M. A., E. A. Callegari, and M. S. Chaussee. Rgg regulates growth phase-dependent expression of proteins associated with secondary metabolism and stress in Streptococcus pyogenes. J Bacteriol 186:7091-9. 2004.
Chaussee, M. A., E. J. McDowell, L. D. Rieck, E. A. Callegari, and M. S. Chaussee. Proteomic analysis of a penicillin-tolerant rgg mutant strain of Streptococcus pyogenes. J Antimicrob Chemother 58:752-9. 2006.
Chaussee, M. S., G. L. Sylva, D. E. Sturdevant, L. M. Smoot, M. R. Graham, R. O. Watson, and J. M. Musser. Rgg influences the expression of multiple regulatory loci to coregulate virulence factor expression in Streptococcus pyogenes. Infect Immun 70:762-70. 2002.
Chen, Y. Y., C. T. Huang, S. M. Yao, Y. C. Chang, P. W. Shen, C. Y. Chou, and S. Y. Li. Molecular epidemiology of group A streptococcus causing scarlet fever in northern Taiwan, 2001-2002. Diagn Microbiol Infect Dis 58:289-95. 2007.
Chiang-Ni, C., C. H. Wang, P. J. Tsai, W. J. Chuang, Y. S. Lin, M. T. Lin, C. C. Liu, and J. J. Wu. Streptococcal pyrogenic exotoxin B causes mitochondria damage to polymorphonuclear cells preventing phagocytosis of group A streptococcus. Med Microbiol Immunol 195:55-63. 2006.
Cleary, P. P., D. LaPenta, R. Vessela, H. Lam, and D. Cue. A globally disseminated M1 subclone of group A streptococci differs from other subclones by 70 kilobases of prophage DNA and capacity for high-frequency intracellular invasion. Infect Immun 66:5592-7. 1998.
Cunningham, M. W. Pathogenesis of group A streptococcal infections. Clin Microbiol Rev 13:470-511. 2000.
Cywes, C., and M. R. Wessels. Group A streptococcus tissue invasion by CD44-mediated cell signalling. Nature 414:648-52. 2001.
Dmitriev, A. V., E. J. McDowell, and M. S. Chaussee. Inter- and intraserotypic variation in the Streptococcus pyogenes Rgg regulon. FEMS Microbiol Lett 284:43-51. 2008.
Dmitriev, A. V., E. J. McDowell, K. V. Kappeler, M. A. Chaussee, L. D. Rieck, and M. S. Chaussee. The Rgg regulator of Streptococcus pyogenes influences utilization of nonglucose carbohydrates, prophage induction, and expression of the NAD-glycohydrolase virulence operon. J Bacteriol 188:7230-41. 2006.
Faruque, S. M., I. B. Naser, M. J. Islam, A. S. Faruque, A. N. Ghosh, G. B. Nair, D. A. Sack, and J. J. Mekalanos. Seasonal epidemics of cholera inversely correlate with the prevalence of environmental cholera phages. Proc Natl Acad Sci U S A 102:1702-7. 2005.
Ferretti, J. J., D. Ajdic, and W. M. McShan. Comparative genomics of streptococcal species. Indian J Med Res 119 Suppl:1-6. 2004.
Ferretti, J. J., W. M. McShan, D. Ajdic, D. J. Savic, G. Savic, K. Lyon, C. Primeaux, S. Sezate, A. N. Suvorov, S. Kenton, H. S. Lai, S. P. Lin, Y. Qian, H. G. Jia, F. Z. Najar, Q. Ren, H. Zhu, L. Song, J. White, X. Yuan, S. W. Clifton, B. A. Roe, and R. McLaughlin. Complete genome sequence of an M1 strain of Streptococcus pyogenes. Proc Natl Acad Sci U S A 98:4658-63. 2001.
Giovanetti, E., A. Brenciani, A. Bacciaglia, M. P. Montanari, and P. E. Varaldo. Expressed and unexpressed tet(M) genes and the erm(B)-carrying Tn1116 transposon in Streptococcus pyogenes and Streptococcus pneumoniae. Antimicrob Agents Chemother 51:4535; author reply 4535-6. 2007.
Graham, M. R., L. M. Smoot, C. A. Migliaccio, K. Virtaneva, D. E. Sturdevant, S. F. Porcella, M. J. Federle, G. J. Adams, J. R. Scott, and J. M. Musser. Virulence control in group A streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling. Proc Natl Acad Sci U S A 99:13855-60. 2002.
Graham, M. R., K. Virtaneva, S. F. Porcella, W. T. Barry, B. B. Gowen, C. R. Johnson, F. A. Wright, and J. M. Musser. Group A streptococcus transcriptome dynamics during growth in human blood reveals bacterial adaptive and survival strategies. Am. J. Pathol. 166:455-65. 2005.
Gryllos, I., R. Grifantini, A. Colaprico, S. Jiang, E. Deforce, A. Hakansson, J. L. Telford, G. Grandi, and M. R. Wessels. Mg(2+) signalling defines the group A streptococcal CsrRS (CovRS) regulon. Mol Microbiol 65:671-83. 2007.
Hauser, A. R., D. L. Stevens, E. L. Kaplan, and P. M. Schlievert. Molecular analysis of pyrogenic exotoxins from Streptococcus pyogenes isolates associated with toxic shock-like syndrome. J Clin Microbiol 29:1562-7. 1991.
Henke, J. M., and B. L. Bassler. Bacterial social engagements. Trends Cell Biol 14:648-56. 2004.
Horstmann, R. D., H. J. Sievertsen, J. Knobloch, and V. A. Fischetti. Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci U S A 85:1657-61. 1988.
Hytonen, J., S. Haataja, D. Gerlach, A. Podbielski, and J. Finne. The SpeB virulence factor of Streptococcus pyogenes, a multifunctional secreted and cell surface molecule with strepadhesin, laminin-binding and cysteine protease activity. Mol Microbiol 39:512-9. 2001.
Ikebe, T., A. Wada, Y. Inagaki, K. Sugama, R. Suzuki, D. Tanaka, A. Tamaru, Y. Fujinaga, Y. Abe, Y. Shimizu, and H. Watanabe. Dissemination of the phage-associated novel superantigen gene speL in recent invasive and noninvasive Streptococcus pyogenes M3/T3 isolates in Japan. Infect Immun 70:3227-33. 2002.
Jadoun, J., V. Ozeri, E. Burstein, E. Skutelsky, E. Hanski, and S. Sela. Protein F1 is required for efficient entry of Streptococcus pyogenes into epithelial cells. J Infect Dis 178:147-58. 1998.
Johnson, L. P., and P. M. Schlievert. Group A streptococcal phage T12 carries the structural gene for pyrogenic exotoxin type A. Mol Gen Genet 194:52-6. 1984.
Jovanovic, G., C. Engl, and M. Buck. Physical, functional and conditional interactions between ArcAB and phage shock proteins upon secretin-induced stress in Escherichia coli. Mol Microbiol 74:16-28. 2009.
Kamezawa, Y., T. Nakahara, S. Nakano, Y. Abe, J. Nozaki-Renard, and T. Isono. Streptococcal mitogenic exotoxin Z, a novel acidic superantigenic toxin produced by a T1 strain of Streptococcus pyogenes. Infect Immun 65:3828-33. 1997.
Kao, C. H., P. Y. Chen, F. L. Huang, C. W. Chen, C. S. Chi, Y. H. Lin, C. Y. Shih, B. S. Hu, C. R. Li, J. S. Ma, Y. J. Lau, K. C. Lu, and H. W. Yu. Clinical and genetic analysis of invasive and non-invasive group A streptococcal infections in central Taiwan. J Microbiol Immunol Infect 38:105-11. 2005.
Kapfhammer, D., J. Blass, S. Evers, and J. Reidl. Vibrio cholerae phage K139: complete genome sequence and comparative genomics of related phages. J Bacteriol 184:6592-601. 2002.
Kappeler, K. V., S. Anbalagan, A. V. Dmitriev, E. J. McDowell, M. N. Neely, and M. S. Chaussee. A naturally occurring Rgg variant in serotype M3 Streptococcus pyogenes does not activate speB expression due to altered specificity of DNA binding. Infect Immun 77:5411-7. 2009.
Kazmi, S. U., R. Kansal, R. K. Aziz, M. Hooshdaran, A. Norrby-Teglund, D. E. Low, A. B. Halim, and M. Kotb. Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group A streptococcal isolates in vivo. Infect Immun 69:4988-95. 2001.
Kloft, N., T. Busch, C. Neukirch, S. Weis, F. Boukhallouk, W. Bobkiewicz, I. Cibis, S. Bhakdi, and M. Husmann. Pore-forming toxins activate MAPK p38 by causing loss of cellular potassium. Biochem Biophys Res Commun 385:503-6. 2009.
Kotb, M. Bacterial pyrogenic exotoxins as superantigens. Clin Microbiol Rev 8:411-26. 1995.
Lancefield, R. C., and V. P. Dole. The Properties of T Antigens Extracted from Group A Hemolytic Streptococci. J Exp Med 84:449-471. 1946.
Levin, J. C., and M. R. Wessels. Identification of csrR/csrS, a genetic locus that regulates hyaluronic acid capsule synthesis in group A streptococcus. Mol Microbiol 30:209-19. 1998.
Loughman, J. A., and M. G. Caparon. A novel adaptation of aldolase regulates virulence in Streptococcus pyogenes. EMBO J 25:5414-22. 2006.
Lyon, W. R., C. M. Gibson, and M. G. Caparon. A role for trigger factor and an rgg-like regulator in the transcription, secretion and processing of the cysteine proteinase of Streptococcus pyogenes. Embo J 17:6263-75. 1998.
Lyon, W. R., J. C. Madden, J. C. Levin, J. L. Stein, and M. G. Caparon. Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes. Mol Microbiol 42:145-57. 2001.
McIver, K. S., A. S. Heath, and J. R. Scott. Regulation of virulence by environmental signals in group A streptococci: influence of osmolarity, temperature, gas exchange, and iron limitation on emm transcription. Infect. Immun. 63:4540-2. 1995.
McIver, K. S., and J. R. Scott. Role of mga in growth phase regulation of virulence genes of the group A streptococcus. J. Bacteriol. 179:5178-87. 1997.
McShan, W. M., and J. J. Ferretti. Genetic studies of erythrogenic toxin carrying temperate bacteriophages of Streptococcus pyogenes. Adv Exp Med Biol 418:971-3. 1997.
McShan, W. M., J. J. Ferretti, T. Karasawa, A. N. Suvorov, S. Lin, B. Qin, H. Jia, S. Kenton, F. Najar, H. Wu, J. Scott, B. A. Roe, and D. J. Savic. Genome sequence of a nephritogenic and highly transformable M49 strain of Streptococcus pyogenes. J Bacteriol 190:7773-85. 2008.
Murray, D. L., D. H. Ohlendorf, and P. M. Schlievert. Staphylococcal and streptococcal superantigens: their role in human disease. ASM News 61:229-235. 1995.
Musser, J. M., A. R. Hauser, M. H. Kim, P. M. Schlievert, K. Nelson, and R. K. Selander. Streptococcus pyogenes causing toxic-shock-like syndrome and other invasive diseases: clonal diversity and pyrogenic exotoxin expression. Proc Natl Acad Sci U S A 88:2668-72. 1991.
Neely, M. N., W. R. Lyon, D. L. Runft, and M. Caparon. Role of RopB in growth phase expression of the SpeB cysteine protease of Streptococcus pyogenes. J Bacteriol 185:5166-74. 2003.
Norrby-Teglund, A., S. E. Holm, and M. Norgren. Detection and nucleotide sequence analysis of the speC gene in Swedish clinical group A streptococcal isolates. J Clin Microbiol 32:705-9. 1994a.
Norrby-Teglund, A., D. Newton, M. Kotb, S. E. Holm, and M. Norgren. Superantigenic properties of the group A streptococcal exotoxin SpeF (MF). Infect Immun 62:5227-33. 1994b.
Norrby-Teglund, A., M. Norgren, S. E. Holm, U. Andersson, and J. Andersson. Similar cytokine induction profiles of a novel streptococcal exotoxin, MF, and pyrogenic exotoxins A and B. Infect Immun 62:3731-8. 1994c.
Norrby-Teglund, A., K. Pauksens, S. E. Holm, and M. Norgren. Relation between low capacity of human sera to inhibit streptococcal mitogens and serious manifestation of disease. J Infect Dis 170:585-91. 1994d.
Ohara, H., K. Uchida, M. Yahata, and H. Kondo. NAD-specific 6-phosphogluconate dehydrogenase in lactic acid bacteria. Biosci Biotechnol Biochem 60:692-3. 1996.
Opdyke, J. A., J. R. Scott, and C. P. Moran, Jr. Expression of the secondary sigma factor sigmaX in Streptococcus pyogenes is restricted at two levels. J Bacteriol 185:4291-7. 2003.
Opdyke, J. A., J. R. Scott, and C. P. Moran, Jr. A secondary RNA polymerase sigma factor from Streptococcus pyogenes. Mol Microbiol 42:495-502. 2001.
Perez-Casal, J., N. Okada, M. G. Caparon, and J. R. Scott. Role of the conserved C-repeat region of the M protein of Streptococcus pyogenes. Mol Microbiol 15:907-16. 1995.
Pinkney, M., V. Kapur, J. Smith, U. Weller, M. Palmer, M. Glanville, M. Messner, J. M. Musser, S. Bhakdi, and M. A. Kehoe. Different forms of streptolysin O produced by Streptococcus pyogenes and by Escherichia coli expressing recombinant toxin: cleavage by streptococcal cysteine protease. Infect Immun 63:2776-9. 1995.
Podbielski, A., M. Woischnik, B. Pohl, and K. H. Schmidt. 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 185:171-81. 1996a.
Podbielski, A., I. Zarges, A. Flosdorff, and J. Weber-Heynemann. Molecular characterization of a major serotype M49 group A streptococcal DNase gene (sdaD). Infect Immun 64:5349-56. 1996b.
Qi, F., P. Chen, and P. W. Caufield. Functional analyses of the promoters in the antibiotic mutacin II biosynthetic locus in Streptococcus mutans. Appl Environ Microbiol 65:652-8. 1999.
Rawlinson, E. L., I. F. Nes, and M. Skaugen. LasX, a transcriptional regulator of the lactocin S biosynthetic genes in Lactobacillus sakei L45, acts both as an activator and a repressor. Biochimie 84:559-67. 2002.
Reda, K. B., V. Kapur, J. A. Mollick, J. G. Lamphear, J. M. Musser, and R. R. Rich. Molecular characterization and phylogenetic distribution of the streptococcal superantigen gene (ssa) from Streptococcus pyogenes. Infect Immun 62:1867-74. 1994.
Reid, S. D., N. M. Green, J. K. Buss, B. Lei, and J. M. Musser. Multilocus analysis of extracellular putative virulence proteins made by group A Streptococcus: population genetics, human serologic response, and gene transcription. Proc Natl Acad Sci U S A 98:7552-7. 2001.
Rigaut, G., A. Shevchenko, B. Rutz, M. Wilm, M. Mann, and B. Seraphin. A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol 17:1030-2. 1999.
Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular Cloning, second ed. Cold Spring Harbor Laboratory Press, New York.
Samen, U. M., B. J. Eikmanns, and D. J. Reinscheid. The transcriptional regulator RovS controls the attachment of Streptococcus agalactiae to human epithelial cells and the expression of virulence genes. Infect Immun 74:5625-35. 2006.
Sanders, J. W., K. Leenhouts, J. Burghoorn, J. R. Brands, G. Venema, and J. Kok. A chloride-inducible acid resistance mechanism in Lactococcus lactis and its regulation. Mol Microbiol 27:299-310. 1998.
Sekiya, K., H. Danbara, and Y. Futaesaku. [Mechanism of pore formation on erythrocyte membrane by streptolysin-O]. Kansenshogaku Zasshi 67:736-40. 1993.
Siller, M., R. P. Janapatla, Z. A. Pirzada, C. Hassler, D. Zinkl, and E. Charpentier. Functional analysis of the group A streptococcal luxS/AI-2 system in metabolism, adaptation to stress and interaction with host cells. BMC Microbiol 8:188. 2008.
Simon, D., and J. J. Ferretti. Electrotransformation of Streptococcus pyogenes with plasmid and linear DNA. FEMS Microbiol Lett 66:219-24. 1991.
Smoot, L. M., J. K. McCormick, J. C. Smoot, N. P. Hoe, I. Strickland, R. L. Cole, K. D. Barbian, C. A. Earhart, D. H. Ohlendorf, L. G. Veasy, H. R. Hill, D. Y. Leung, P. M. Schlievert, and J. M. Musser. Characterization of two novel pyrogenic toxin superantigens made by an acute rheumatic fever clone of Streptococcus pyogenes associated with multiple disease outbreaks. Infect Immun 70:7095-104. 2002.
Steer, A. C., I. Law, L. Matatolu, B. W. Beall, and J. R. Carapetis. Global emm type distribution of group A streptococci: systematic review and implications for vaccine development. Lancet Infect Dis 9:611-6. 2009.
Stevens, D. L. Invasive group A streptococcus infections. Clin Infect Dis 14:2-11. 1992.
Storz, G., and R. Hengge-Aronis. 2000. Bacterial stress responses. American society of Microbiology, Washington, DC.
Su, Y. F., S. M. Wang, Y. L. Lin, W. J. Chuang, Y. S. Lin, J. J. Wu, M. T. Lin, and C. C. Liu. Changing epidemiology of Streptococcus pyogenes emm types and associated invasive and noninvasive infections in Southern Taiwan. J Clin Microbiol 47:2658-61. 2009.
Sulavik, M. C., and D. B. Clewell. Rgg is a positive transcriptional regulator of the Streptococcus gordonii gtfG gene. J Bacteriol 178:5826-30. 1996.
Sumby, P., S. F. Porcella, A. G. Madrigal, K. D. Barbian, K. Virtaneva, S. M. Ricklefs, D. E. Sturdevant, M. R. Graham, J. Vuopio-Varkila, N. P. Hoe, and J. M. Musser. Evolutionary origin and emergence of a highly successful clone of serotype M1 group A streptococcus involved multiple horizontal gene transfer events. J Infect Dis 192:771-82. 2005.
Sumby, P., and M. K. Waldor. Transcription of the toxin genes present within the Staphylococcal phage phiSa3ms is intimately linked with the phage's life cycle. J Bacteriol 185:6841-51. 2003.
Suvorov, A. N., E. M. Polyakova, W. M. McShan, and J. J. Ferretti. Bacteriophage content of M49 strains of Streptococcus pyogenes. FEMS Microbiol Lett 294:9-15. 2009.
Talkington, D. F., B. Schwartz, C. M. Black, J. K. Todd, J. Elliott, R. F. Breiman, and R. R. Facklam. Association of phenotypic and genotypic characteristics of invasive Streptococcus pyogenes isolates with clinical components of streptococcal toxic shock syndrome. Infect Immun 61:3369-74. 1993.
Tsou, C. C., C. Chiang-Ni, Y. S. Lin, W. J. Chuang, M. T. Lin, C. C. Liu, and J. J. Wu. An iron-binding protein, Dpr, decreases hydrogen peroxide stress and protects Streptococcus pyogenes against multiple stresses. Infect Immun 76:4038-45. 2008.
Tsou, C. C., C. Chiang-Ni, Y. S. Lin, W. J. Chuang, M. T. Lin, C. C. Liu, and J. J. Wu. Oxidative stress and metal ions regulate a ferritin-like gene, dpr, in Streptococcus pyogenes. Int J Med Microbiol. 2009.
Uchiyama, T., X. J. Yan, K. Imanishi, and J. Yagi. Bacterial superantigens--mechanism of T cell activation by the superantigens and their role in the pathogenesis of infectious diseases. Microbiol Immunol 38:245-56. 1994.
Wagner, P. L., J. Livny, M. N. Neely, D. W. Acheson, D. I. Friedman, and M. K. Waldor. Bacteriophage control of Shiga toxin 1 production and release by Escherichia coli. Mol Microbiol 44:957-70. 2002.
Wagner, P. L., and M. K. Waldor. Bacteriophage control of bacterial virulence. Infect Immun 70:3985-93. 2002.
Whitnack, E., and E. H. Beachey. Biochemical and biological properties of the binding of human fibrinogen to M protein in group A streptococci. J Bacteriol 164:350-8. 1985.
Woodbury, R. L., X. Wang, and C. P. Moran, Jr. Sigma X induces competence gene expression in Streptococcus pyogenes. Res Microbiol 157:851-6. 2006.
Xu, S., and C. M. Collins. Temperature regulation of the streptococcal pyrogenic exotoxin A-encoding gene (speA). Infect Immun 64:5399-402. 1996.