Skip to main content

Common Regulators of Virulence in Streptococci

  • Chapter
  • First Online:
Book cover Host-Pathogen Interactions in Streptococcal Diseases

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 368))

Abstract

Streptococcal species are a diverse group of bacteria which can be found in animals and humans. Their interactions with host organisms can vary from commensal to pathogenic. Many of the pathogenic species are causative agents of severe, invasive infections in their hosts, accounting for a high burden of morbidity and mortality, associated with high economic costs in industry and health care. Among them, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus suis are discussed here. An environmentally stimulated and tightly controlled expression of their virulence factors is of utmost importance for their pathogenic potential. Thus, the most universal and widespread regulators from the classes of stand-alone transcriptional regulators, two-component signal transduction systems (TCS), eukaryotic-like serine/threonine kinases, and small noncoding RNAs are the topic of this chapter. The regulatory levels are reviewed with respect to function, activity, and their role in pathogenesis. Understanding of and interfering with transcriptional regulation mechanisms and networks is a promising basis for the development of novel anti-infective therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Acebo P, Martin-Galiano AJ, Navarro S, Zaballos A, Amblar M (2012) Identification of 88 regulatory small RNAs in the TIGR4 strain of the human pathogen Streptococcus pneumoniae. RNA 18:530–546

    Article  PubMed  CAS  Google Scholar 

  • Agarwal S, Agarwal S, Pancholi P, Pancholi V (2011) Role of serine/threonine phosphatase (SP-STP) in Streptococcus pyogenes physiology and virulence. J Biol Chem 286:41368–41380

    Article  PubMed  CAS  Google Scholar 

  • Agarwal S, Agarwal S, Pancholi P, Pancholi V (2012) Strain-specific regulatory role of eukaryote-like serine/threonine phosphatase in pneumococcal adherence. Infect Immun 80:1361–1372

    Article  PubMed  CAS  Google Scholar 

  • Ahmed NA, Petersen FC, Scheie AA (2008) Biofilm formation and autoinducer-2 signaling in Streptococcus intermedius: role of thermal and pH factors. Oral Microbiol Immunol 23:492–497

    Article  PubMed  CAS  Google Scholar 

  • Almengor AC, McIver KS (2004) Transcriptional activation of sclA by Mga requires a distal binding site in Streptococcus pyogenes. J Bacteriol 186:7847–7857

    Article  PubMed  CAS  Google Scholar 

  • Almengor AC, Walters MS, McIver KS (2006) Mga is sufficient to activate transcription in vitro of sof-sfbX and other Mga-regulated virulence genes in the group A Streptococcus. J Bacteriol 188:2038–2047

    Article  PubMed  CAS  Google Scholar 

  • Almengor AC, Kinkel TL, Day SJ, McIver KS (2007) 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

    Article  PubMed  CAS  Google Scholar 

  • Antunes LC, Ferreira RB, Buckner MM, Finlay BB (2010) Quorum sensing in bacterial virulence. Microbiology 156:2271–2282

    Article  PubMed  CAS  Google Scholar 

  • Arnvig KB, Young DB (2009) Identification of small RNAs in Mycobacterium tuberculosis. Mol Microbiol 73:397–408

    Article  PubMed  CAS  Google Scholar 

  • Aziz RK, Kansal R, Aronow BJ, Taylor WL, Rowe SL, Kubal M, Chhatwal GS, Walker MJ, Kotb M (2010) Microevolution of group A streptococci in vivo: capturing regulatory networks engaged in sociomicrobiology, niche adaptation, and hypervirulence. PLoS One 5:e9798

    Article  PubMed  CAS  Google Scholar 

  • Basset A, Turner KH, Boush E, Sayeed S, Dove SL, Malley R (2011) Expression of the type 1 pneumococcal pilus is bistable and negatively regulated by the structural component RrgA. Infect Immun 79:2974–2983

    Article  PubMed  CAS  Google Scholar 

  • Basset A, Turner KH, Boush E, Sayeed S, Dove SL, Malley R (2012) An epigenetic switch mediates bistable expression of the type 1 pilus genes in Streptococcus pneumoniae. J Bacteriol 194:1088–1091

    Article  PubMed  CAS  Google Scholar 

  • Bastet L, Dube A, Masse E, Lafontaine DA (2011) New insights into riboswitch regulation mechanisms. Mol Microbiol 80:1148–1154

    Article  PubMed  CAS  Google Scholar 

  • Beaume M, Hernandez D, Docquier M, Delucinge-Vivier C, Descombes P, Francois P (2011) Orientation and expression of methicillin-resistant Staphylococcus aureus small RNAs by direct multiplexed measurements using the nCounter of NanoString technology. J Microbiol Methods 84:327–334

    Article  PubMed  CAS  Google Scholar 

  • Beckert S, Kreikemeyer B, Podbielski A (2001) Group A streptococcal rofA gene is involved in the control of several virulence genes and eukaryotic cell attachment and internalization. Infect Immun 69:534–537

    Article  PubMed  CAS  Google Scholar 

  • Bernish B, van de Rijn I (1999) Characterization of a two-component system in Streptococcus pyogenes which is involved in regulation of hyaluronic acid production. J Biol Chem 274:4786–4793

    Article  PubMed  CAS  Google Scholar 

  • Bessen DE, Hollingshead SK (1994) Allelic polymorphism of emm loci provides evidence for horizontal gene spread in group A streptococci. Proc Natl Acad Sci U S A 91:3280–3284

    Article  PubMed  CAS  Google Scholar 

  • Bessen DE, Lizano S (2010) Tissue tropisms in group A streptococcal infections. Future Microbiol 5:623–638

    Article  PubMed  Google Scholar 

  • Bessen DE, Manoharan A, Luo F, Wertz JE, Robinson DA (2005) Evolution of transcription regulatory genes is linked to niche specialization in the bacterial pathogen Streptococcus pyogenes. J Bacteriol 187:4163–4172

    Article  PubMed  CAS  Google Scholar 

  • Betschel SD, Borgia SM, Barg NL, Low DE, De Azavedo JC (1998) Reduced virulence of group A streptococcal Tn916 mutants that do not produce streptolysin S. Infect Immun 66:1671–1679

    PubMed  CAS  Google Scholar 

  • Biswas I, Germon P, McDade K, Scott JR (2001) Generation and surface localization of intact M protein in Streptococcus pyogenes are dependent on sagA. Infect Immun 69:7029–7038

    Article  PubMed  CAS  Google Scholar 

  • Blehert DS, Palmer RJ Jr, Xavier JB, Almeida JS, Kolenbrander PE (2003) Autoinducer 2 production by Streptococcus gordonii DL1 and the biofilm phenotype of a luxS mutant are influenced by nutritional conditions. J Bacteriol 185:4851–4860

    Article  PubMed  CAS  Google Scholar 

  • Blount KF, Breaker RR (2006) Riboswitches as antibacterial drug targets. Nat Biotechnol 24:1558–1564

    Article  PubMed  CAS  Google Scholar 

  • Brantl S (2009) Bacterial chromosome-encoded small regulatory RNAs. Future Microbiol 4:85–103

    Article  PubMed  CAS  Google Scholar 

  • Bryan J, Liles R, Cvek U, Trutschl M, Shelver D (2008) Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor. BMC Genomics 9:607

    Article  PubMed  CAS  Google Scholar 

  • Burnside K, Rajagopal L (2011) Aspects of eukaryotic-like signaling in gram-positive cocci: a focus on virulence. Future Microbiol 6:747–761

    Article  PubMed  CAS  Google Scholar 

  • Burnside K, Lembo A, Harrell MI, Gurney M, Xue L, BinhTran NT, Connelly JE, Jewell KA, Schmidt BZ, de los RM, Tao WA, Doran KS, Rajagopal L (2011) Serine/threonine phosphatase Stp1 mediates post-transcriptional regulation of hemolysin, autolysis, and virulence of group B Streptococcus. J Biol Chem 286:44197–44210

    Google Scholar 

  • Cao M, Feng Y, Wang C, Zheng F, Li M, Liao H, Mao Y, Pan X, Wang J, Hu D, Hu F, Tang J (2011) Functional definition of LuxS, an autoinducer-2 (AI-2) synthase and its role in full virulence of Streptococcus suis serotype 2. J Microbiol 49:1000–1011

    Article  PubMed  CAS  Google Scholar 

  • Caparon MG, Scott JR (1987) Identification of a gene that regulates expression of M protein, the major virulence determinant of group A streptococci. Proc Natl Acad Sci U S A 84:8677–8681

    Article  PubMed  CAS  Google Scholar 

  • Carapetis JR, Steer AC, Mulholland EK, Weber M (2005) The global burden of group A streptococcal diseases. Lancet Infect Dis 5:685–694

    Article  PubMed  Google Scholar 

  • Carvalho SM, Kloosterman TG, Kuipers OP, Neves AR (2011) CcpA ensures optimal metabolic fitness of Streptococcus pneumoniae. PLoS One 6:e26707

    Article  PubMed  CAS  Google Scholar 

  • Caymaris S, Bootsma HJ, Martin B, Hermans PW, Prudhomme M, Claverys JP (2010) The global nutritional regulator CodY is an essential protein in the human pathogen Streptococcus pneumoniae. Mol Microbiol 78:344–360

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Tang J, Dong W, Wang C, Feng Y, Wang J, Zheng F, Pan X, Liu D, Li M, Song Y, Zhu X, Sun H, Feng T, Guo Z, Ju A, Ge J, Dong Y, Sun W, Jiang Y, Wang J, Yan J, Yang H, Wang X, Gao GF, Yang R, Wang J, Yu J (2007) A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates. PLoS One 2:e315

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Indurthi DC, Jones SW, Papoutsakis ET (2011) Small RNAs in the genus Clostridium. MBio 2:00340–0010

    CAS  Google Scholar 

  • Christensen T, Johnsen M, Fiil NP, Friesen JD (1984) RNA secondary structure and translation inhibition: analysis of mutants in the rplJ leader. EMBO J 3:1609–1612

    PubMed  CAS  Google Scholar 

  • Churchward G (2007) The two faces of Janus: virulence gene regulation by CovR/S in group A streptococci. Mol Microbiol 64:34–41

    Article  PubMed  CAS  Google Scholar 

  • Cunningham MW (2000) Pathogenesis of group A streptococcal infections. Clin Microbiol Rev 13:470–511

    Article  PubMed  CAS  Google Scholar 

  • Dramsi S, Dubrac S, Konto-Ghiorghi Y, Da C, V, Couve E, Glaser P, Caliot E, Debarbouille M, Bellais S, Trieu-Cuot P, Mistou MY (2012) Rga, a RofA-like regulator, is the major transcriptional activator of the PI-2a pilus in Streptococcus agalactiae. Microb Drug Resist 18:286–297

    Google Scholar 

  • Dalton TL, Collins JT, Barnett TC, Scott JR (2006) RscA, a member of the MDR1 family of transporters, is repressed by CovR and required for growth of Streptococcus pyogenes under heat stress. J Bacteriol 188:77–85

    Article  PubMed  CAS  Google Scholar 

  • Danne C, Entenza JM, Mallet A, Briandet R, Debarbouille M, Nato F, Glaser P, Jouvion G, Moreillon P, Trieu-Cuot P, Dramsi S (2011) Molecular characterization of a Streptococcus gallolyticus genomic island encoding a pilus involved in endocarditis. J Infect Dis 204:1960–1970

    Article  PubMed  CAS  Google Scholar 

  • De Angelis G, Moschioni M, Muzzi A, Pezzicoli A, Censini S, Delany I, Lo SM, Sinisi A, Donati C, Masignani V, Barocchi MA (2011) The Streptococcus pneumoniae pilus-1 displays a biphasic expression pattern. PLoS One 6:e21269

    Article  PubMed  CAS  Google Scholar 

  • Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y, Pirzada ZA, Eckert MR, Vogel J, Charpentier E (2011) CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471:602–607

    Article  PubMed  CAS  Google Scholar 

  • Dramsi S, Caliot E, Bonne I, Guadagnini S, Prevost MC, Kojadinovic M, Lalioui L, Poyart C, Trieu-Cuot P (2006) Assembly and role of pili in group B streptococci. Mol Microbiol 60:1401–1413

    Article  PubMed  CAS  Google Scholar 

  • Echenique J, Kadioglu A, Romao S, Andrew PW, Trombe MC (2004) Protein serine/threonine kinase StkP positively controls virulence and competence in Streptococcus pneumoniae. Infect Immun 72:2434–2437

    Article  PubMed  CAS  Google Scholar 

  • Federle MJ (2009) Autoinducer-2-based chemical communication in bacteria: complexities of interspecies signaling. Contrib Microbiol 16:18–32

    Article  PubMed  CAS  Google Scholar 

  • Federle MJ, Bassler BL (2003) Interspecies communication in bacteria. J Clin Invest 112:1291–1299

    PubMed  CAS  Google Scholar 

  • Fiedler T, Sugareva V, Patenge N, Kreikemeyer B (2010a) Insights into Streptococcus pyogenes pathogenesis from transcriptome studies. Future Microbiol 5:1675–1694

    Article  PubMed  CAS  Google Scholar 

  • Fiedler T, Kreikemeyer B, Sugareva V, Redanz S, Arlt R, Standar K, Podbielski A (2010b) Impact of the Streptococcus pyogenes Mga regulator on human matrix protein binding and interaction with eukaryotic cells. Int J Med Microbiol 300:248–258

    Article  PubMed  CAS  Google Scholar 

  • Fittipaldi N, Takamatsu D, de la Cruz Dominguez-Punaro, Lecours MP, Montpetit D, Osaki M, Sekizaki T, Gottschalk M (2010) Mutations in the gene encoding the ancillary pilin subunit of the Streptococcus suis srtF cluster result in pili formed by the major subunit only. PLoS One 5:e8426

    Google Scholar 

  • Fittipaldi N, Segura M, Grenier D, Gottschalk M (2012) Virulence factors involved in the pathogenesis of the infection caused by the swine pathogen and zoonotic agent Streptococcus suis. Future Microbiol 7:259–279

    Article  PubMed  CAS  Google Scholar 

  • Froehlich BJ, Bates C, Scott JR (2009) Streptococcus pyogenes CovRS mediates growth in iron starvation and in the presence of the human cationic antimicrobial peptide LL-37. J Bacteriol 191:673–677

    Article  PubMed  CAS  Google Scholar 

  • Frohlich KS, Vogel J (2009) Activation of gene expression by small RNA. Curr Opin Microbiol 12:674–682

    Article  PubMed  CAS  Google Scholar 

  • Gamez G, Hammerschmidt S (2012) Combat pneumococcal infections: adhesins as candidates for protein- based vaccine development. Curr Drug Targets 13:323–337

    Article  PubMed  CAS  Google Scholar 

  • Gao J, Gusa AA, Scott JR, Churchward G (2005) Binding of the global response regulator protein CovR to the sag promoter of Streptococcus pyogenes reveals a new mode of CovR-DNA interaction. J Biol Chem 280:38948–38956

    Article  PubMed  CAS  Google Scholar 

  • Gardner PP, Daub J, Tate JG, Nawrocki EP, Kolbe DL, Lindgreen S, Wilkinson AC, Finn RD, Griffiths-Jones S, Eddy SR, Bateman A (2009) Rfam: updates to the RNA families database. Nucleic Acids Res 37:D136–D140

    Article  PubMed  CAS  Google Scholar 

  • Gasiunas G, Barrangou R, Horvath P, Siksnys V (2012) Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci U S A 109:E2579–E2586

    Article  PubMed  CAS  Google Scholar 

  • Giammarinaro P, Paton JC (2002) Role of RegM, a homologue of the catabolite repressor protein CcpA, in the virulence of Streptococcus pneumoniae. Infect Immun 70:5454–5461

    Article  PubMed  CAS  Google Scholar 

  • Glaser P, Rusniok C, Buchrieser C, Chevalier F, Frangeul L, Msadek T, Zouine M, Couve E, Lalioui L, Poyart C, Trieu-Cuot P, Kunst F (2002) Genome sequence of Streptococcus agalactiae, a pathogen causing invasive neonatal disease. Mol Microbiol 45:1499–1513

    Article  PubMed  CAS  Google Scholar 

  • Gogol EB, Rhodius VA, Papenfort K, Vogel J, Gross CA (2011) Small RNAs endow a transcriptional activator with essential repressor functions for single-tier control of a global stress regulon. Proc Natl Acad Sci U S A 108:12875–12880

    Article  PubMed  CAS  Google Scholar 

  • Gorke B, Vogel J (2008) Noncoding RNA control of the making and breaking of sugars. Genes Dev 22:2914–2925

    Article  PubMed  CAS  Google Scholar 

  • Gottesman S and Storz G (2011) Bacterial small RNA regulators: versatile roles and rapidly evolving variations. Cold Spring Harb Perspect Biol 3:a003798

    Google Scholar 

  • Gottesman S, McCullen CA, Guillier M, Vanderpool CK, Majdalani N, Benhammou J, Thompson KM, FitzGerald PC, Sowa NA, FitzGerald DJ (2006) Small RNA regulators and the bacterial response to stress. Cold Spring Harb Symp Quant Biol 71:1–11

    Article  PubMed  CAS  Google Scholar 

  • Graham MR, Virtaneva K, Porcella SF, Barry WT, Gowen BB, Johnson CR, Wright FA, Musser JM (2005) Group A Streptococcus transcriptome dynamics during growth in human blood reveals bacterial adaptive and survival strategies. Am J Pathol 166:455–465

    Article  PubMed  CAS  Google Scholar 

  • Granok AB, Parsonage D, Ross RP, Caparon MG (2000) The RofA binding site in Streptococcus pyogenes is utilized in multiple transcriptional pathways. J Bacteriol 182:1529–1540

    Article  PubMed  CAS  Google Scholar 

  • Gryllos I, Grifantini R, Colaprico A, Jiang S, Deforce E, Hakansson A, Telford JL, Grandi G, Wessels MR (2007) Mg(2 +) signalling defines the group A streptococcal CsrRS (CovRS) regulon. Mol Microbiol 65:671–683

    Article  PubMed  CAS  Google Scholar 

  • Guedon E, Sperandio B, Pons N, Ehrlich SD, Renault P (2005) Overall control of nitrogen metabolism in Lactococcus lactis by CodY, and possible models for CodY regulation in Firmicutes. Microbiology 151:3895–3909

    Article  PubMed  CAS  Google Scholar 

  • Guenzi E, Gasc AM, Sicard MA, Hakenbeck R (1994) A two-component signal-transducing system is involved in competence and penicillin susceptibility in laboratory mutants of Streptococcus pneumoniae. Mol Microbiol 12:505–515

    Article  PubMed  CAS  Google Scholar 

  • Gusa AA, Scott JR (2005) The CovR response regulator of group A streptococcus (GAS) acts directly to repress its own promoter. Mol Microbiol 56:1195–1207

    Article  PubMed  CAS  Google Scholar 

  • Gusa AA, Gao J, Stringer V, Churchward G, Scott JR (2006) Phosphorylation of the group A Streptococcal CovR response regulator causes dimerization and promoter-specific recruitment by RNA polymerase. J Bacteriol 188:4620–4626

    Article  PubMed  CAS  Google Scholar 

  • Gutekunst H, Eikmanns BJ, Reinscheid DJ (2003) Analysis of RogB-controlled virulence mechanisms and gene expression in Streptococcus agalactiae. Infect Immun 71:5056–5064

    Article  PubMed  CAS  Google Scholar 

  • Haanes EJ, Heath DG, Cleary PP (1992) Architecture of the vir regulons of group A streptococci parallels opacity factor phenotype and M protein class. J Bacteriol 174:4967–4976

    PubMed  CAS  Google Scholar 

  • Haft DH, Selengut J, Mongodin EF, Nelson KE (2005) A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes. PLoS Comput Biol 1:e60

    Article  PubMed  CAS  Google Scholar 

  • Halfmann A, Kovacs M, Hakenbeck R, Bruckner R (2007) Identification of the genes directly controlled by the response regulator CiaR in Streptococcus pneumoniae: five out of 15 promoters drive expression of small non-coding RNAs. Mol Microbiol 66:110–126

    Article  PubMed  CAS  Google Scholar 

  • Halfmann A, Schnorpfeil A, Muller M, Marx P, Gunzler U, Hakenbeck R, Bruckner R (2011) Activity of the two-component regulatory system CiaRH in Streptococcus pneumoniae R6. J Mol Microbiol Biotechnol 20:96–104

    Article  PubMed  CAS  Google Scholar 

  • Han XG, Lu CP (2009) Detection of autoinducer-2 and analysis of the profile of luxS and pfs transcription in Streptococcus suis serotype 2. Curr Microbiol 58:146–152

    Article  PubMed  CAS  Google Scholar 

  • Han H, Liu C, Wang Q, Xuan C, Zheng B, Tang J, Yan J, Zhang J, Li M, Cheng H, Lu G, Gao GF (2012) The two-component system Ihk/Irr contributes to the virulence of Streptococcus suis serotype 2 strain 05ZYH33 through alteration of the bacterial cell metabolism. Microbiology 158:1852–1866

    Article  PubMed  CAS  Google Scholar 

  • Hava DL, Camilli A (2002) Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol Microbiol 45:1389–1406

    PubMed  CAS  Google Scholar 

  • Hava DL, Hemsley CJ, Camilli A (2003) Transcriptional regulation in the Streptococcus pneumoniae rlrA pathogenicity islet by RlrA. J Bacteriol 185:413–421

    Article  PubMed  CAS  Google Scholar 

  • Heath A, DiRita VJ, Barg NL, Engleberg NC (1999) 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 67:5298–5305

    PubMed  CAS  Google Scholar 

  • Heidrich N, Chinali A, Gerth U, Brantl S (2006) The small untranslated RNA SR1 from the Bacillus subtilis genome is involved in the regulation of arginine catabolism. Mol Microbiol 62:520–536

    Article  PubMed  CAS  Google Scholar 

  • Hemsley C, Joyce E, Hava DL, Kawale A, Camilli A (2003) MgrA, an orthologue of Mga, acts as a transcriptional repressor of the genes within the rlrA pathogenicity islet in Streptococcus pneumoniae. J Bacteriol 185:6640–6647

    Article  PubMed  CAS  Google Scholar 

  • Hendriksen WT, Bootsma HJ, Estev + úo S, Hoogenboezem T, de Jong A, de Groot R, Kuipers OP, Hermans PWM (2008) CodY of Streptococcus pneumoniae: link between nutritional gene regulation and colonization. J Bacteriol 190:590–601

    Google Scholar 

  • Hertzen E, Johansson L, Kansal R, Hecht A, Dahesh S, Janos M, Nizet V, Kotb M, Norrby-Teglund A (2012) Intracellular Streptococcus pyogenes in human macrophages display an altered gene expression profile. PLoS One 7:e35218

    Article  PubMed  CAS  Google Scholar 

  • Hoch JA (2000) Two-component and phosphorelay signal transduction. Curr Opin Microbiol 3:165–170

    Article  PubMed  CAS  Google Scholar 

  • Hollingshead SK, Bessen DE (1995) Evolution of the emm gene family: virulence gene clusters in group A streptococci. Dev Biol Stand 85:163–168

    PubMed  CAS  Google Scholar 

  • Hollingshead SK, Readdy TL, Yung DL, Bessen DE (1993) Structural heterogeneity of the emm gene cluster in group A streptococci. Mol Microbiol 8:707–717

    Article  PubMed  CAS  Google Scholar 

  • Hondorp ER, McIver KS (2007) The Mga virulence regulon: infection where the grass is greener. Mol Microbiol 66:1056–1065

    Article  PubMed  CAS  Google Scholar 

  • Hoskins J, Alborn WE Jr, Arnold J, Blaszczak LC, Burgett S, DeHoff BS, Estrem ST, Fritz L, Fu DJ, Fuller W, Geringer C, Gilmour R, Glass JS, Khoja H, Kraft AR, Lagace RE, LeBlanc DJ, Lee LN, Lefkowitz EJ, Lu J, Matsushima P, McAhren SM, McHenney M, McLeaster K, Mundy CW, Nicas TI, Norris FH, O’Gara M, Peery RB, Robertson GT, Rockey P, Sun PM, Winkler ME, Yang Y, Young-Bellido M, Zhao G, Zook CA, Baltz RH, Jaskunas SR, Rosteck PR Jr, Skatrud PL, Glass JI (2001) Genome of the bacterium Streptococcus pneumoniae strain R6. J Bacteriol 183:5709–5717

    Article  PubMed  CAS  Google Scholar 

  • Iyer R, Baliga NS, Camilli A (2005) Catabolite control protein A (CcpA) contributes to virulence and regulation of sugar metabolism in Streptococcus pneumoniae. J Bacteriol 187:8340–8349

    Article  PubMed  CAS  Google Scholar 

  • Jiang SM, Cieslewicz MJ, Kasper DL, Wessels MR (2005) Regulation of virulence by a two-component system in group B streptococcus. J Bacteriol 187:1105–1113

    Article  PubMed  CAS  Google Scholar 

  • Jiang SM, Ishmael N, Dunning HJ, Puliti M, Tissi L, Kumar N, Cieslewicz MJ, Tettelin H, Wessels MR (2008) Variation in the group B Streptococcus CsrRS regulon and effects on pathogenicity. J Bacteriol 190:1956–1965

    Article  PubMed  CAS  Google Scholar 

  • Jin H, Pancholi V (2006) Identification and biochemical characterization of a eukaryotic-type serine/threonine kinase and its cognate phosphatase in Streptococcus pyogenes: their biological functions and substrate identification. J Mol Biol 357:1351–1372

    Article  PubMed  CAS  Google Scholar 

  • Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–821

    Article  PubMed  CAS  Google Scholar 

  • Johansson J, Mandin P, Renzoni A, Chiaruttini C, Springer M, Cossart P (2002) An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell 110:551–561

    Article  PubMed  Google Scholar 

  • Johnsen M, Christensen T, Dennis PP, Fiil NP (1982) Autogenous control: ribosomal protein L10–L12 complex binds to the leader sequence of its mRNA. EMBO J 1:999–1004

    PubMed  CAS  Google Scholar 

  • Joyce EA, Kawale A, Censini S, Kim CC, Covacci A, Falkow S (2004) LuxS is required for persistent pneumococcal carriage and expression of virulence and biosynthesis genes. Infect Immun 72:2964–2975

    Article  PubMed  CAS  Google Scholar 

  • Kaufman GE, Yother J (2007) CcpA-dependent and -independent control of beta-galactosidase expression in Streptococcus pneumoniae occurs via regulation of an upstream phosphotransferase system-encoding operon. J Bacteriol 189:5183–5192

    Article  PubMed  CAS  Google Scholar 

  • Kazmierczak KM, Wayne KJ, Rechtsteiner A, Winkler ME (2009) Roles of relSpn in stringent response, global regulation and virulence of serotype 2 Streptococcus pneumoniae D39. Mol Microbiol 72:590–611

    Article  PubMed  CAS  Google Scholar 

  • Kietzman CC, Caparon MG (2010) CcpA and LacD.1 affect temporal regulation of Streptococcus pyogenes virulence genes. Infect Immun 78:241–252

    Article  PubMed  CAS  Google Scholar 

  • Kietzman CC, Caparon MG (2011) Distinct time-resolved roles for two catabolite-sensing pathways during Streptococcus pyogenes infection. Infect Immun 79:812–821

    Article  PubMed  CAS  Google Scholar 

  • Kihlberg BM, Cooney J, Caparon MG, Olsen A, Bjorck L (1995) Biological properties of a Streptococcus pyogenes mutant generated by Tn916 insertion in mga. Microb Pathog 19:299–315

    Article  PubMed  CAS  Google Scholar 

  • Kinkel TL, McIver KS (2008) CcpA-mediated repression of streptolysin s expression and virulence in the group A Streptococcus. Infect Immun 76:3451–3463

    Article  PubMed  CAS  Google Scholar 

  • Klenk M, Koczan D, Guthke R, Nakata M, Thiesen HJ, Podbielski A, Kreikemeyer B (2005) Global epithelial cell transcriptional responses reveal Streptococcus pyogenes Fas regulator activity association with bacterial aggressiveness. Cell Microbiol 7:1237–1250

    Article  PubMed  CAS  Google Scholar 

  • Klinkert B, Narberhaus F (2009) Microbial thermosensors. Cell Mol Life Sci 66:2661–2676

    Article  PubMed  CAS  Google Scholar 

  • Kratovac Z, Manoharan A, Luo F, Lizano S, Bessen DE (2007) Population genetics and linkage analysis of loci within the FCT region of Streptococcus pyogenes. J Bacteriol 189:1299–1310

    Article  PubMed  CAS  Google Scholar 

  • Kreikemeyer B, Boyle MD, Buttaro BA, Heinemann M, 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 39:392–406

    Article  PubMed  CAS  Google Scholar 

  • Kreikemeyer B, McIver KS, Podbielski A (2003) Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen-host interactions. Trends Microbiol 11:224–232

    Article  PubMed  CAS  Google Scholar 

  • Kreikemeyer B, Nakata M, Koller T, Hildisch H, Kourakos V, Standar K, Kawabata S, Glocker MO, Podbielski A (2007) The Streptococcus pyogenes serotype M49 Nra-Ralp3 transcriptional regulatory network and its control of virulence factor expression from the novel eno ralp3 epf sagA pathogenicity region. Infect Immun 75:5698–5710

    Article  PubMed  CAS  Google Scholar 

  • Kreikemeyer B, Gamez G, Margarit I, Giard JC, Hammerschmidt S, Hartke A, 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

    Article  PubMed  CAS  Google Scholar 

  • Kreth J, Chen Z, Ferretti J, Malke H (2011) Counteractive balancing of transcriptome expression involving CodY and CovRS in Streptococcus pyogenes. J Bacteriol 193:4153–4165

    Article  PubMed  CAS  Google Scholar 

  • Kumar R, Shah P, Swiatlo E, Burgess SC, Lawrence ML, Nanduri B (2010) Identification of novel non-coding small RNAs from Streptococcus pneumoniae TIGR4 using high-resolution genome tiling arrays. BMC Genomics 11:350

    Article  PubMed  CAS  Google Scholar 

  • Lamy MC, Zouine M, Fert J, Vergassola M, Couve E, Pellegrini E, Glaser P, Kunst F, Msadek T, Trieu-Cuot P, Poyart C (2004) CovS/CovR of group B streptococcus: a two-component global regulatory system involved in virulence. Mol Microbiol 54:1250–1268

    Article  PubMed  CAS  Google Scholar 

  • Lanie JA, Ng WL, Kazmierczak KM, Andrzejewski TM, Davidsen TM, Wayne KJ, Tettelin H, Glass JI, Winkler ME (2007) Genome sequence of Avery’s virulent serotype 2 strain D39 of Streptococcus pneumoniae and comparison with that of unencapsulated laboratory strain R6. J Bacteriol 189:38–51

    Article  PubMed  CAS  Google Scholar 

  • Le Rhun A, Charpentier E (2012) Small RNAs in streptococci. RNA Biol 9:414–426

    Article  PubMed  CAS  Google Scholar 

  • Leday TV, Gold KM, Kinkel TL, Roberts SA, Scott JR, McIver KS (2008) TrxR, a new CovR-repressed response regulator that activates the Mga virulence regulon in group A Streptococcus. Infect Immun 76:4659–4668

    Article  PubMed  CAS  Google Scholar 

  • Lee ER, Blount KF, Breaker RR (2009) Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression. RNA Biol 6:187–194

    Article  PubMed  CAS  Google Scholar 

  • Levin JC, Wessels MR (1998) Identification of csrR/csrS, a genetic locus that regulates hyaluronic acid capsule synthesis in group A Streptococcus. Mol Microbiol 30:209–219

    Article  PubMed  CAS  Google Scholar 

  • Li Z, Sledjeski DD, Kreikemeyer B, Podbielski A, Boyle MD (1999) Identification of pel, a Streptococcus pyogenes locus that affects both surface and secreted proteins. J Bacteriol 181:6019–6027

    PubMed  CAS  Google Scholar 

  • Li N, Wang F, Niu S, Cao J, Wu K, Li Y, Yin N, Zhang X, Zhu W, Yin Y (2009) Discovery of novel inhibitors of Streptococcus pneumoniae based on the virtual screening with the homology-modeled structure of histidine kinase (VicK). BMC Microbiol 9:129

    Article  PubMed  CAS  Google Scholar 

  • Li W, Liu L, Qiu D, Chen H, Zhou R (2010) Identification of Streptococcus suis serotype 2 genes preferentially expressed in the natural host. Int J Med Microbiol 300:482–488

    Article  PubMed  CAS  Google Scholar 

  • Li J, Tan C, Zhou Y, Fu S, Hu L, Hu J, Chen H, Bei W (2011) The two-component regulatory system CiaRH contributes to the virulence of Streptococcus suis 2. Vet Microbiol 148:99–104

    Article  PubMed  CAS  Google Scholar 

  • Liu M, Hanks TS, Zhang J, McClure MJ, Siemsen DW, Elser JL, Quinn MT, Lei B (2006) Defects in ex vivo and in vivo growth and sensitivity to osmotic stress of group A Streptococcus caused by interruption of response regulator gene vicR. Microbiology 152:967–978

    Article  PubMed  CAS  Google Scholar 

  • Liu Z, Trevino J, Ramirez-Pena E, Sumby P (2012) The small regulatory RNA FasX controls pilus expression and adherence in the human bacterial pathogen group A Streptococcus. Mol Microbiol 86:140–154

    Article  PubMed  CAS  Google Scholar 

  • Livny J, Waldor MK (2007) Identification of small RNAs in diverse bacterial species. Curr Opin Microbiol 10:96–101

    Article  PubMed  CAS  Google Scholar 

  • Livny J, Fogel MA, Davis BM, Waldor MK (2005) sRNAPredict: an integrative computational approach to identify sRNAs in bacterial genomes. Nucleic Acids Res 33:4096–4105

    Article  PubMed  CAS  Google Scholar 

  • Livny J, Brencic A, Lory S, Waldor MK (2006) Identification of 17 Pseudomonas aeruginosa sRNAs and prediction of sRNA-encoding genes in 10 diverse pathogens using the bioinformatic tool sRNAPredict2. Nucleic Acids Res 34:3484–3493

    Article  PubMed  CAS  Google Scholar 

  • Loh E, Dussurget O, Gripenland J, Vaitkevicius K, Tiensuu T, Mandin P, Repoila F, Buchrieser C, Cossart P, Johansson J (2009) A trans-acting riboswitch controls expression of the virulence regulator PrfA in Listeria monocytogenes. Cell 139:770–779

    Article  PubMed  CAS  Google Scholar 

  • Loughman JA, Caparon MG (2006) A novel adaptation of aldolase regulates virulence in Streptococcus pyogenes. EMBO J 25:5414–5422

    Article  PubMed  CAS  Google Scholar 

  • Loughman JA, Caparon MG (2007) Comparative functional analysis of the lac operons in Streptococcus pyogenes. Mol Microbiol 64:269–280

    Article  PubMed  CAS  Google Scholar 

  • Luo F, Lizano S, Banik S, Zhang H, Bessen DE (2008) Role of Mga in group A streptococcal infection at the skin epithelium. Microb Pathog 45:217–224

    Article  PubMed  CAS  Google Scholar 

  • Lyon WR, Madden JC, Levin JC, Stein JL, Caparon MG (2001) Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes. Mol Microbiol 42:145–157

    Article  PubMed  CAS  Google Scholar 

  • Malke H, Ferretti JJ (2007) CodY-affected transcriptional gene expression of Streptococcus pyogenes during growth in human blood. J Med Microbiol 56:707–714

    Article  PubMed  CAS  Google Scholar 

  • Malke H, Steiner K, McShan WM, Ferretti JJ (2006) Linking the nutritional status of Streptococcus pyogenes to alteration of transcriptional gene expression: the action of CodY and RelA. Int J Med Microbiol 296:259–275

    Article  PubMed  CAS  Google Scholar 

  • Manetti AG, Koller T, Becherelli M, Buccato S, Kreikemeyer B, Podbielski A, Grandi G, 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

    Article  PubMed  CAS  Google Scholar 

  • Mangold M, Siller M, Roppenser B, Vlaminckx BJ, Penfound TA, Klein R, Novak R, Novick RP, Charpentier E (2004) Synthesis of group A streptococcal virulence factors is controlled by a regulatory RNA molecule. Mol Microbiol 53:1515–1527

    Article  PubMed  CAS  Google Scholar 

  • Mann B, van OT, Wang J, Obert C, Wang YD, Carter R, McGoldrick DJ, Ridout G, Camilli A, Tuomanen EI, Rosch JW (2012) Control of Virulence by Small RNAs in Streptococcus pneumoniae. PLoS Pathog 8:e1002788

    Google Scholar 

  • Mansjo M, Johansson J (2011) The riboflavin analog roseoflavin targets an FMN-riboswitch and blocks Listeria monocytogenes growth, but also stimulates virulence gene-expression and infection. RNA Biol 8:674–680

    Article  PubMed  CAS  Google Scholar 

  • Marouni MJ, Sela S (2003) The luxS Gene of Streptococcus pyogenes regulates expression of genes that affect internalization by epithelial cells. Infect Immun 71:5633–5639

    Article  PubMed  CAS  Google Scholar 

  • Marraffini LA, Sontheimer EJ (2010) Self versus non-self discrimination during CRISPR RNA-directed immunity. Nature 463:568–571

    Article  PubMed  CAS  Google Scholar 

  • Marx P, Nuhn M, Kovacs M, Hakenbeck R, Bruckner R (2010) Identification of genes for small non-coding RNAs that belong to the regulon of the two-component regulatory system CiaRH in Streptococcus. BMC Genomics 11:661

    Article  PubMed  CAS  Google Scholar 

  • Mascher T, Zahner D, Merai M, Balmelle N, de Saizieu AB, Hakenbeck R (2003) The Streptococcus pneumoniae cia regulon: CiaR target sites and transcription profile analysis. J Bacteriol 185:60–70

    Article  PubMed  CAS  Google Scholar 

  • Mascher T, Heintz M, Zahner D, Merai M, Hakenbeck R (2006) The CiaRH system of Streptococcus pneumoniae prevents lysis during stress induced by treatment with cell wall inhibitors and by mutations in pbp2x involved in beta-lactam resistance. J Bacteriol 188:1959–1968

    Article  PubMed  CAS  Google Scholar 

  • McIver KS (2009) Stand-alone response regulators controlling global virulence networks in Streptococcus pyogenes. Contrib Microbiol 16:103–119

    Article  PubMed  CAS  Google Scholar 

  • McIver KS, Scott JR (1997) Role of mga in growth phase regulation of virulence genes of the group A Streptococcus. J Bacteriol 179:5178–5187

    PubMed  CAS  Google Scholar 

  • McIver KS, Heath AS, Green BD, Scott JR (1995) Specific binding of the activator Mga to promoter sequences of the emm and scpA genes in the group A Streptococcus. J Bacteriol 177:6619–6624

    PubMed  CAS  Google Scholar 

  • McIver KS, Thurman AS, Scott JR (1999) Regulation of mga transcription in the group A Streptococcus: specific binding of mga within its own promoter and evidence for a negative regulator. J Bacteriol 181:5373–5383

    PubMed  CAS  Google Scholar 

  • Mistou MY, Dramsi S, Brega S, Poyart C, Trieu-Cuot P (2009) Molecular dissection of the secA2 locus of group B Streptococcus reveals that glycosylation of the Srr1 LPXTG protein is required for full virulence. J Bacteriol 191:4195–4206

    Article  PubMed  CAS  Google Scholar 

  • Mitchell AM, Mitchell TJ (2010) Streptococcus pneumoniae: virulence factors and variation. Clin Microbiol Infect 16:411–418

    Article  PubMed  CAS  Google Scholar 

  • Mraheil MA, Billion A, Kuenne C, Pischimarov J, Kreikemeyer B, Engelmann S, Hartke A, Giard JC, Rupnik M, Vorwerk S, Beier M, Retey J, Hartsch T, Jacob A, Cemic F, Hemberger J, Chakraborty T, Hain T (2010) Comparative genome-wide analysis of small RNAs of major Gram-positive pathogens: from identification to application. Microb Biotechnol 3:658–676

    Article  PubMed  CAS  Google Scholar 

  • Mraheil MA, Billion A, Mohamed W, Mukherjee K, Kuenne C, Pischimarov J, Krawitz C, Retey J, Hartsch T, Chakraborty T, Hain T (2011) The intracellular sRNA transcriptome of Listeria monocytogenes during growth in macrophages. Nucleic Acids Res 39:4235–4248

    Article  PubMed  CAS  Google Scholar 

  • Muller M, Marx P, Hakenbeck R, Bruckner R (2011) Effect of new alleles of the histidine kinase gene ciaH on the activity of the response regulator CiaR in Streptococcus pneumoniae R6. Microbiology 157:3104–3112

    Article  PubMed  CAS  Google Scholar 

  • Nakata M, Podbielski A, Kreikemeyer B (2005) MsmR, a specific positive regulator of the Streptococcus pyogenes FCT pathogenicity region and cytolysin-mediated translocation system genes. Mol Microbiol 57:786–803

    Article  PubMed  CAS  Google Scholar 

  • Nakata M, Koller T, Moritz K, Ribardo D, Jonas L, McIver KS, Sumitomo T, Terao Y, Kawabata S, Podbielski A, Kreikemeyer B (2009) Mode of expression and functional characterization of FCT-3 pilus region-encoded proteins in Streptococcus pyogenes serotype M49. Infect Immun 77:32–44

    Article  PubMed  CAS  Google Scholar 

  • Narberhaus F, Vogel J (2009) Regulatory RNAs in prokaryotes: here, there and everywhere. Mol Microbiol 74:261–269

    Article  PubMed  CAS  Google Scholar 

  • Novick RP, Ross HF, Projan SJ, Kornblum J, Kreiswirth B, Moghazeh S (1993) Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. EMBO J 12:3967–3975

    PubMed  CAS  Google Scholar 

  • Nudler E, Mironov AS (2004) The riboswitch control of bacterial metabolism. Trends Biochem Sci 29:11–17

    Article  PubMed  CAS  Google Scholar 

  • Okada N, Geist RT, Caparon MG (1993) Positive transcriptional control of mry regulates virulence in the group A streptococcus. Mol Microbiol 7:893–903

    Article  PubMed  CAS  Google Scholar 

  • Ou YQ, Ma WL, Liu CH, Shi R, Zheng WL (2005) [Detection of quorum-sensing pathway and construction of LuxS gene deletion mutants of group B Streptococcus]. Di Yi Jun Yi Da Xue Xue Bao 25:1135–1139

    Google Scholar 

  • Ouyang Q, Ma WL, Liu CH, Shi R, Zheng WL (2006) [Phenotypic analysis of luxS gene deletion mutants and its application in virulence regulation research in group B Streptococcus]. Nan Fang Yi Ke Da Xue Xue Bao 26:117–121

    Google Scholar 

  • Pan X, Ge J, Li M, Wu B, Wang C, Wang J, Feng Y, Yin Z, Zheng F, Cheng G, Sun W, Ji H, Hu D, Shi P, Feng X, Hao X, Dong R, Hu F, Tang J (2009) The orphan response regulator CovR: a globally negative modulator of virulence in Streptococcus suis serotype 2. J Bacteriol 191:2601–2612

    Article  PubMed  CAS  Google Scholar 

  • Papenfort K, Vogel J (2010) Regulatory RNA in bacterial pathogens. Cell Host Microbe 8:116–127

    Article  PubMed  CAS  Google Scholar 

  • Park SE, Jiang S, Wessels MR (2012) CsrRS and environmental pH regulate group B Streptococcus adherence to human epithelial cells and extracellular matrix. Infect Immun 80:3975−3984

    Google Scholar 

  • Patenge N, Billion A, Raasch P, Normann J, Wisniewska-Kucper A, Retey J, Boisguérin V, Hartsch T, Hain T, Kreikemeyer B (2012) Identification of novel growth phase- and media-dependent small non-coding RNAs in Streptococcus pyogenes M49 using intergenic tiling arrays. BMC Genomics 13:550

    Google Scholar 

  • Paterson GK, Blue CE, Mitchell TJ (2006) Role of two-component systems in the virulence of Streptococcus pneumoniae. J Med Microbiol 55:355–363

    Article  PubMed  CAS  Google Scholar 

  • Perez N, Trevino J, Liu Z, Ho SC, Babitzke P, Sumby P (2009) A genome-wide analysis of small regulatory RNAs in the human pathogen group A Streptococcus. PLoS One 4:e7668

    Article  PubMed  CAS  Google Scholar 

  • Perez-Casal JF, Dillon HF, Husmann LK, Graham B, Scott JR (1993) Virulence of two Streptococcus pyogenes strains (types M1 and M3) associated with toxic-shock-like syndrome depends on an intact mry-like gene. Infect Immun 61:5426–5430

    PubMed  CAS  Google Scholar 

  • Petersen FC, Ahmed NA, Naemi A, Scheie AA (2006) LuxS-mediated signalling in Streptococcus anginosus and its role in biofilm formation. Antonie Van Leeuwenhoek 90:109–121

    Google Scholar 

  • Pichon C, du ML, Caliot ME, Trieu-Cuot P, Le BC (2012) An in silico model for identification of small RNAs in whole bacterial genomes: characterization of antisense RNAs in pathogenic Escherichia coli and Streptococcus agalactiae strains. Nucleic Acids Res 40:2846–2861

    Google Scholar 

  • Pischimarov J, Kuenne C, Billion A, Hemberger J, Cemic F, Chakraborty T, Hain T (2012) sRNAdb: A small non-coding RNA database for gram-positive bacteria. BMC Genomics 13:384

    Article  PubMed  CAS  Google Scholar 

  • Podbielski A, Flosdorff A, Weber-Heynemann J (1995) The group A streptococcal virR49 gene controls expression of four structural vir regulon genes. Infect Immun 63:9–20

    PubMed  CAS  Google Scholar 

  • Podbielski A, Woischnik M, Leonard BA, Schmidt KH (1999) Characterization of nra, a global negative regulator gene in group A streptococci. Mol Microbiol 31:1051–1064

    Article  PubMed  CAS  Google Scholar 

  • Podkaminski D, Vogel J (2010) Small RNAs promote mRNA stability to activate the synthesis of virulence factors. Mol Microbiol 78:1327–1331

    Article  PubMed  CAS  Google Scholar 

  • Price CE, Zeyniyev A, Kuipers OP, Kok J (2011) From meadows to milk to mucosa—adaptation of Streptococcus and Lactococcus species to their nutritional environments. FEMS Microbiol Rev 36:949–971

    Google Scholar 

  • Quach D, van Sorge NM, Kristian SA, Bryan JD, Shelver DW, Doran KS (2009) The CiaR response regulator in group B Streptococcus promotes intracellular survival and resistance to innate immune defenses. J Bacteriol 191:2023–2032

    Article  PubMed  CAS  Google Scholar 

  • Raasch P, Schmitz U, Patenge N, Vera J, Kreikemeyer B, Wolkenhauer O (2010) Non-coding RNA detection methods combined to improve usability, reproducibility and precision. BMC Bioinform 11:491

    Article  CAS  Google Scholar 

  • Rajagopal L (2009) Understanding the regulation of Group B Streptococcal virulence factors. Future Microbiol 4:201–221

    Article  PubMed  CAS  Google Scholar 

  • Rajagopal L, Clancy A, Rubens CE (2003) A eukaryotic type serine/threonine kinase and phosphatase in Streptococcus agalactiae reversibly phosphorylate an inorganic pyrophosphatase and affect growth, cell segregation, and virulence. J Biol Chem 278:14429–14441

    Article  PubMed  CAS  Google Scholar 

  • Rajagopal L, Vo A, Silvestroni A, Rubens CE (2006) Regulation of cytotoxin expression by converging eukaryotic-type and two-component signalling mechanisms in Streptococcus agalactiae. Mol Microbiol 62:941–957

    Article  PubMed  CAS  Google Scholar 

  • Ramirez-Pena E, Trevino J, Liu Z, Perez N, Sumby P (2010) The group A Streptococcus small regulatory RNA FasX enhances streptokinase activity by increasing the stability of the ska mRNA transcript. Mol Microbiol 78:1332–1347

    Article  PubMed  CAS  Google Scholar 

  • Redanz S, Standar K, Podbielski A, Kreikemeyer B (2012) Heterologous expression of sahH reveals that biofilm formation is autoinducer-2 independent in Streptococcus sanguinis, but is associated with an intact AMC. J Biol Chem 287:36111−36122

    Google Scholar 

  • Riani C, Standar K, Srimuang S, Lembke C, Kreikemeyer B, Podbielski A (2007) Transcriptome analyses extend understanding of Streptococcus pyogenes regulatory mechanisms and behavior toward immunomodulatory substances. Int J Med Microbiol 297:513–523

    Article  PubMed  CAS  Google Scholar 

  • Ribardo DA, McIver KS (2003) amrA encodes a putative membrane protein necessary for maximal exponential phase expression of the Mga virulence regulon in Streptococcus pyogenes. Mol Microbiol 50:673–685

    Article  PubMed  CAS  Google Scholar 

  • Ribardo DA, McIver KS (2006) Defining the Mga regulon: comparative transcriptome analysis reveals both direct and indirect regulation by Mga in the group A Streptococcus. Mol Microbiol 62:491–508

    Article  PubMed  CAS  Google Scholar 

  • Roberts SA, Scott JR (2007) RivR and the small RNA RivX: the missing links between the CovR regulatory cascade and the Mga regulon. Mol Microbiol 66:1506–1522

    PubMed  CAS  Google Scholar 

  • Romao S, Memmi G, Oggioni MR, Trombe MC (2006) LuxS impacts on LytA-dependent autolysis and on competence in Streptococcus pneumoniae. Microbiology 152:333–341

    Article  PubMed  CAS  Google Scholar 

  • Rosch JW, Mann B, Thornton J, Sublett J, Tuomanen E (2008) Convergence of regulatory networks on the pilus locus of Streptococcus pneumoniae. Infect Immun 76:3187–3196

    Article  PubMed  CAS  Google Scholar 

  • Samen U, Heinz B, Boisvert H, Eikmanns BJ, Reinscheid DJ, Borges F (2011) Rga is a regulator of adherence and pilus formation in Streptococcus agalactiae. Microbiology 157:2319–2327

    Article  PubMed  CAS  Google Scholar 

  • Santi I, Grifantini R, Jiang SM, Brettoni C, Grandi G, Wessels MR, Soriani M (2009) CsrRS regulates group B Streptococcus virulence gene expression in response to environmental pH: a new perspective on vaccine development. J Bacteriol 191:5387–5397

    Article  PubMed  CAS  Google Scholar 

  • Sapranauskas R, Gasiunas G, Fremaux C, Barrangou R, Horvath P, Siksnys V (2011) The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. Nucleic Acids Res 39:9275–9282

    Article  PubMed  CAS  Google Scholar 

  • Schauder S, Shokat K, Surette MG, Bassler BL (2001) The LuxS family of bacterial autoinducers: biosynthesis of a novel quorum-sensing signal molecule. Mol Microbiol 41:463–476

    Article  PubMed  CAS  Google Scholar 

  • Scott JR, Zahner D (2006) Pili with strong attachments: Gram-positive bacteria do it differently. Mol Microbiol 62:320–330

    Article  PubMed  CAS  Google Scholar 

  • Sebert ME, Patel KP, Plotnick M, Weiser JN (2005) Pneumococcal HtrA protease mediates inhibition of competence by the CiaRH two-component signaling system. J Bacteriol 187:3969–3979

    Article  PubMed  CAS  Google Scholar 

  • Sharma CM, Hoffmann S, Darfeuille F, Reignier J, Findeiss S, Sittka A, Chabas S, Reiche K, Hackermuller J, Reinhardt R, Stadler PF, Vogel J (2010) The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464:250–255

    Article  PubMed  CAS  Google Scholar 

  • Sharma CM, Papenfort K, Pernitzsch SR, Mollenkopf HJ, Hinton JC, Vogel J (2011) Pervasive post-transcriptional control of genes involved in amino acid metabolism by the Hfq-dependent GcvB small RNA. Mol Microbiol 81:1144–1165

    Article  PubMed  CAS  Google Scholar 

  • Shelburne SA III, Sumby P, Sitkiewicz I, Granville C, Deleo FR, Musser JM (2005) Central role of a bacterial two-component gene regulatory system of previously unknown function in pathogen persistence in human saliva. Proc Natl Acad Sci U S A 102:16037–16042

    Article  PubMed  CAS  Google Scholar 

  • Shelburne SA, Keith D, Horstmann N, Sumby P, Davenport MT, Graviss EA, Brennan RG, Musser JM (2008) A direct link between carbohydrate utilization and virulence in the major human pathogen group A Streptococcus. Proc Natl Acad Sci 105:1698–1703

    Article  PubMed  CAS  Google Scholar 

  • Shelburne SA, Olsen RJ, Suber B, Sahasrabhojane P, Sumby P, Brennan RG, Musser JM (2010) A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection. PLoS Pathog 6:e1000817

    Article  PubMed  CAS  Google Scholar 

  • Shelver D, Rajagopal L, Harris TO, Rubens CE (2003) MtaR, a regulator of methionine transport, is critical for survival of group B Streptococcus in vivo. J Bacteriol 185:6592–6599

    Article  PubMed  CAS  Google Scholar 

  • Siller M, Janapatla R, Pirzada Z, Hassler C, Zinkl D, Charpentier E (2008) 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

    Article  PubMed  CAS  Google Scholar 

  • Solano-Collado V, Espinosa M, Bravo A (2012) Activator role of the pneumococcal mga-like virulence transcriptional regulator. J Bacteriol 194:4197–4207

    Article  PubMed  CAS  Google Scholar 

  • Sonenshein AL (2005) CodY, a global regulator of stationary phase and virulence in gram-positive bacteria. Curr Opin Microbiol 8:203–207

    Article  PubMed  CAS  Google Scholar 

  • Sridhar J, Sambaturu N, Sabarinathan R, Ou HY, Deng Z, Sekar K, Rafi ZA, Rajakumar K (2010) sRNAscanner: a computational tool for intergenic small RNA detection in bacterial genomes. PLoS One 5:e11970

    Article  PubMed  CAS  Google Scholar 

  • Stenz L, Francois P, Whiteson K, Wolz C, Linder P, Schrenzel J (2011) The CodY pleiotropic repressor controls virulence in gram-positive pathogens. FEMS Immunol Med Microbiol 62:123–139

    Article  PubMed  CAS  Google Scholar 

  • Stock AM, Robinson VL, Goudreau PN (2000) Two-component signal transduction. Annu Rev Biochem 69:183–215

    Article  PubMed  CAS  Google Scholar 

  • Storz G, Vogel J, Wassarman KM (2011) Regulation by small RNAs in bacteria: expanding frontiers. Mol Cell 43:880–891

    Article  PubMed  CAS  Google Scholar 

  • Stroeher UH, Paton AW, Ogunniyi AD, Paton JC (2003) Mutation of luxS of Streptococcus pneumoniae affects virulence in a mouse model. Infect Immun 71:3206–3212

    Article  PubMed  CAS  Google Scholar 

  • Sugareva V, Arlt R, Fiedler T, Riani C, Podbielski A, Kreikemeyer B (2010) Serotype- and strain- dependent contribution of the sensor kinase CovS of the CovRS two-component system to Streptococcus pyogenes pathogenesis. BMC Microbiol 10:34

    Article  PubMed  CAS  Google Scholar 

  • Sumby P, Whitney AR, Graviss EA, DeLeo FR, Musser JM (2006) Genome-wide analysis of group A Streptococci reveals a mutation that modulates global phenotype and disease specificity. PLoS Pathog 2:e5

    Article  PubMed  CAS  Google Scholar 

  • Surette MG, Miller MB, Bassler BL (1999) Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: a new family of genes responsible for autoinducer production. Proc Natl Acad Sci U S A 96:1639–1644

    Article  PubMed  CAS  Google Scholar 

  • Takamatsu D, Nishino H, Ishiji T, Ishii J, Osaki M, Fittipaldi N, Gottschalk M, Tharavichitkul P, Takai S, Sekizaki T (2009) Genetic organization and preferential distribution of putative pilus gene clusters in Streptococcus suis. Vet Microbiol 138:132–139

    Article  PubMed  CAS  Google Scholar 

  • Telford JL, Barocchi MA, Margarit I, Rappuoli R, Grandi G (2006) Pili in gram-positive pathogens. Nat Rev Microbiol 4:509–519

    Article  PubMed  CAS  Google Scholar 

  • Tettelin H, Nelson KE, Paulsen IT, Eisen JA, Read TD, Peterson S, Heidelberg J, Deboy RT, Haft DH, Dodson RJ, Durkin AS, Gwinn M, Kolonay JF, Nelson WC, Peterson JD, Umayam LA, White O, Salzberg SL, Lewis MR, Radune D, Holtzapple E, Khouri H, Wolf AM, Utterback TR, Hansen CL, McDonald LA, Feldblyum TV, Angiuoli S, Dickinson T, Hickey EK, Holt IE, Loftus BJ, Yang F, Smith HO, Venter JC, Dougherty BA, Morrison DA, Hollingshead SK, Fraser CM (2001) Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293:498–506

    Article  PubMed  CAS  Google Scholar 

  • Tettelin H, Masignani V, Cieslewicz MJ, Eisen JA, Peterson S, Wessels MR, Paulsen IT, Nelson KE, Margarit I, Read TD, Madoff LC, Wolf AM, Beanan MJ, Brinkac LM, Daugherty SC, Deboy RT, Durkin AS, Kolonay JF, Madupu R, Lewis MR, Radune D, Fedorova NB, Scanlan D, Khouri H, Mulligan S, Carty HA, Cline RT, Van Aken SE, Gill J, Scarselli M, Mora M, Iacobini ET, Brettoni C, Galli G, Mariani M, Vegni F, Maione D, Rinaudo D, Rappuoli R, Telford JL, Kasper DL, Grandi G, Fraser CM (2002) Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae. Proc Natl Acad Sci U S A 99:12391–12396

    Article  PubMed  CAS  Google Scholar 

  • Thomason MK, Storz G (2010) Bacterial antisense RNAs: how many are there, and what are they doing? Annu Rev Genet 44:167–188

    Article  PubMed  CAS  Google Scholar 

  • Trappetti C, Potter AJ, Paton AW, Oggioni MR, Paton JC (2011) LuxS mediates iron-dependent biofilm formation, competence, and fratricide in Streptococcus pneumoniae. Infect Immun 79:4550–4558

    Article  PubMed  CAS  Google Scholar 

  • Trevino J, Perez N, Ramirez-Pena E, Liu Z, Shelburne SA III, Musser JM, Sumby P (2009) CovS simultaneously activates and inhibits the CovR-mediated repression of distinct subsets of group A Streptococcus virulence factor-encoding genes. Infect Immun 77:3141–3149

    Article  PubMed  CAS  Google Scholar 

  • Trevino J, Perez N, Sumby P (2010) The 4.5S RNA component of the signal recognition particle is required for group A Streptococcus virulence. Microbiology 156:1342–1350

    Article  PubMed  CAS  Google Scholar 

  • Tsui HC, Mukherjee D, Ray VA, Sham LT, Feig AL, Winkler ME (2010) Identification and characterization of noncoding small RNAs in Streptococcus pneumoniae serotype 2 strain D39. J Bacteriol 192:264–279

    Article  PubMed  CAS  Google Scholar 

  • Vahling CM, McIver KS (2006) Domains required for transcriptional activation show conservation in the mga family of virulence gene regulators. J Bacteriol 188:863–873

    Article  PubMed  CAS  Google Scholar 

  • Vanderpool CK, Gottesman S (2005) Noncoding RNAs at the membrane. Nat Struct Mol Biol 12:285–286

    Article  PubMed  CAS  Google Scholar 

  • Vendeville A, Winzer K, Heurlier K, Tang CM, Hardie KR (2005) Making ‘sense’ of metabolism: autoinducer-2, LuxS and pathogenic bacteria. Nat Rev Microbiol 3:383–396

    Article  PubMed  CAS  Google Scholar 

  • Vidal JE, Ludewick HP, Kunkel RM, Zähner D, Klugman KP (2011) The LuxS-dependent quorum-sensing system regulates early biofilm formation by Streptococcus pneumoniae strain D39. Infect Immun 79:4050–4060

    Article  PubMed  CAS  Google Scholar 

  • Vitreschak AG, Rodionov DA, Mironov AA, Gelfand MS (2002) Regulation of riboflavin biosynthesis and transport genes in bacteria by transcriptional and translational attenuation. Nucleic Acids Res 30:3141–3151

    Article  PubMed  CAS  Google Scholar 

  • Voyich JM, Sturdevant DE, Braughton KR, Kobayashi SD, Lei B, Virtaneva K, Dorward DW, Musser JM, Deleo FR (2003) Genome-wide protective response used by group A Streptococcus to evade destruction by human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A 100:1996–2001

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Zhang W, Wu Z, Zhu X, Lu C (2011) Functional analysis of luxS in Streptococcus suis reveals a key role in biofilm formation and virulence. Vet Microbiol 152:151–160

    Article  PubMed  CAS  Google Scholar 

  • Waters LS, Storz G (2009) Regulatory RNAs in bacteria. Cell 136:615–628

    Article  PubMed  CAS  Google Scholar 

  • Willenborg J, Fulde M, de Greeff A, Rohde M, Smith HE, Valentin-Weigand P, Goethe R (2011) Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis. Microbiology 157:1823–1833

    Article  PubMed  CAS  Google Scholar 

  • Winkler ME, Hoch JA (2008) Essentiality, bypass, and targeting of the YycFG (VicRK) two-component regulatory system in gram-positive bacteria. J Bacteriol 190:2645–2648

    Article  PubMed  CAS  Google Scholar 

  • Xia L, Xia W, Li S, Li W, Liu J, Ding H, Li J, Li H, Chen Y, Su X, Wang W, Sun L, Wang C, Shao N, Chu B (2012) Identification and expression of small non-coding RNA, L10-Leader, in different growth phases of Streptococcus mutans. Nucleic Acid Ther 22:177–186

    PubMed  CAS  Google Scholar 

  • Yoshida A, Ansai T, Takehara T, Kuramitsu HK (2005) LuxS-based signaling affects Streptococcus mutans biofilm formation. Appl Environ Microbiol 71:2372–2380

    Article  PubMed  CAS  Google Scholar 

  • Zahner D, Kaminski K, van der Linden M, Mascher T, Meral M, Hakenbeck R (2002) The ciaR/ciaH regulatory network of Streptococcus pneumoniae. J Mol Microbiol Biotechnol 4:211–216

    PubMed  CAS  Google Scholar 

  • Zahner D, Gandhi AR, Yi H, Stephens DS (2011) Mitis group streptococci express variable pilus islet 2 pili. PLoS One 6:25124

    Article  CAS  Google Scholar 

  • Zhu J, Patel R, Pei D (2004) Catalytic mechanism of S-ribosylhomocysteinase (LuxS): stereochemical course and kinetic isotope effect of proton transfer reactions. Biochemistry 43:10166–10172

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bernd Kreikemeyer .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Patenge, N., Fiedler, T., Kreikemeyer, B. (2012). Common Regulators of Virulence in Streptococci. In: Chhatwal, G. (eds) Host-Pathogen Interactions in Streptococcal Diseases. Current Topics in Microbiology and Immunology, vol 368. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2012_295

Download citation

Publish with us

Policies and ethics