TrxR, a new CovR-repressed response regulator that activates the Mga virulence regulon in group A streptococcus

Infection and Immunity

Volumn 76, Issue 10, 2008, Pages 4659-4668

  Leday, Temekka V ^a   Gold, Kathryn M ^b   Kinkel, Traci L ^a,b   Roberts, Samantha A ^c,d   Scott, June R ^c   McIver, Kevin S ^a,b  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b University of Maryland   (United States)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d CENTER FOR BIOLOGICS EVALUATION AND RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LUCIFERASE; VIRULENCE FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BACTERIAL GENE; BACTERIAL GENETICS; BACTERIAL STRAIN; BACTERIAL VIRULENCE; CONTROLLED STUDY; DISEASE SEVERITY; DNA MICROARRAY; EXPERIMENTAL MODEL; EXPERIMENTAL MOUSE; GENE ACTIVATION; GENE EXPRESSION; GENE FUNCTION; GENE FUSION; GENE INSERTION; GENE MUTATION; GENE REPRESSION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LETHALITY; MGA VIRULENCE REGULON; MICROARRAY ANALYSIS; MOUSE; NONHUMAN; OPERON; PLASMID; PRIORITY JOURNAL; PROMOTER REGION; REGULATOR GENE; REGULATORY MECHANISM; REGULON; REPORTER GENE; SEQUENCE HOMOLOGY; SKIN INFECTION; STREPTOCOCCUS GROUP A; STREPTOCOCCUS PNEUMONIAE; TRXR GENE; WILD TYPE;

ANIMALS; ARTIFICIAL GENE FUSION; BACTERIAL PROTEINS; GENE DELETION; GENES, REPORTER; GENETIC COMPLEMENTATION TEST; LUCIFERASES; MICE; MUTAGENESIS, INSERTIONAL; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; REGULON; REPRESSOR PROTEINS; SKIN DISEASES, BACTERIAL; STREPTOCOCCAL INFECTIONS; STREPTOCOCCUS PYOGENES; SURVIVAL ANALYSIS; TRANSCRIPTION FACTORS; VIRULENCE; VIRULENCE FACTORS;

EID: 53649092162     PISSN: 00199567     EISSN: None     Source Type: Journal    
DOI: 10.1128/IAI.00597-08     Document Type: Article

References (50)

1. Aziz, R. K., R. A. Edwards, W. W. Taylor, D. E. Low, A. McGeer, and M. Kotb. 2005. Mosaic prophages with horizontally acquired genes account for the emergence and diversification of the globally disseminated M1T1 clone of Streptococcus pyogenes. J. Bacteriol. 187:3311-3318.
2. Banks, D. J., S. F. Porcella, K. D. Barbian, S. B. Beres, L. E. Philips, J. M. Voyich, F. R. DeLeo, J. M. Martin, G. A. Somerville, and J. M. Musser. 2004. Progress toward characterization of the group A Streptococcus metagenome: complete genome sequence of a macrolide-resistant serotype M6 strain. J. Infect. Dis. 190:727-738.
3. Beckert, S., B. Kreikemeyer, and A. Podbielski. 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.
4. Beres, S. B., E. W. Richter, M. J. Nagiec, P. Sumby, S. F. Porcella, F. R. DeLeo, and J. M. Musser. 2006. Molecular genetic anatomy of inter- and intraserotype variation in the human bacterial pathogen group A Streptococcus. Proc. Natl. Acad. Sci. USA 103:7059-7064.
5. 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. 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.
6. Chaussee, M. S., D. Ajdic, and J. J. Ferretti. 1999. The rgg gene of Streptococcus pyogenes NZ131 positively influences extracellular SPE B production. Infect. Immun. 67:1715-1722.
7. Churchward, G. 2007. The two faces of Janus: virulence gene regulation by CovR/S in group A streptococci. Mol. Microbiol. 64:34-41.
8. Cunningham, M. W. 2000. Pathogenesis of group A streptococcal infections. Clin. Microbiol. Rev. 13:470-511.
9. Dalton, T. L., J. T. Collins, T. C. Barnett, and J. R. Scott. 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.
10. Dalton, T. L., R. I. Hobb, and J. R. Scott. 2006. Analysis of the role of CovR and CovS in the dissemination of Streptococcus pyogenes in invasive skin disease. Microb. Pathog. 40:221-227.
11. Dalton, T. L., and J. R. Scott. 2004. CovS inactivates CovR and is required for growth under conditions of general stress in Streptococcus pyogenes. J. Bacteriol. 186:3928-3937.
12. Federle, M. J., K. S. McIver, and J. R. Scott. 1999. A response regulator that represses transcription of several virulence operons in the group A streptococcus. J. Bacteriol. 181:3649-3657.
13. 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. 2001. Complete genome sequence of an M1 strain of Streptococcus pyogenes. Proc. Natl. Acad. Sci. USA 98:4658-4663.
14. Gao, J., A. A. Gusa, J. R. Scott, and G. Churchward. 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.
15. 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. 2002. 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. USA 99:13855-13860.
16. Green, N. M., S. Zhang, S. F. Porcella, M. J. Nagiec, K. D. Barbian, S. B. Beres, R. B. Lefebvre, and J. M. Musser. 2005. Genome sequence of a serotype M28 strain of group A streptococcus: potential new insights into puerperal sepsis and bacterial disease specificity. J. Infect. Dis. 192:760-770.
17. 2+ signalling defines the group A streptococcal CsrRS (CovRS) regulon. Mol. Microbiol. 65:671-683.
18. 2+. Proc. Natl. Acad. Sci. USA 100:4227-4232.
19. Gusa, A. A., and J. R. Scott. 2005. The CovR response regulator of group A streptococcus (GAS) acts directly to repress its own promoter. Mol. Microbiol. 56:1195-1207.
20. Hava, D. L., and A. Camilli. 2002. Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol. Microbiol. 45:1389-1406.
21. Heath, A., V. J. DiRita, N. L. Barg, and N. C. Engleberg. 1999. A twocomponent 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.
22. Hondorp, E. R., and K. S. McIver. 2007. The Mga virulence regulon: infection where the grass is greener. Mol. Microbiol. 66:1056-1065.
23. Kinkel, T. L., and K. S. McIver. 2008. CcpA-mediated repression of streptolysin S expression and virulence in the group A streptococcus. Infect. Immun. 76:3451-3463.
24. Kreikemeyer, B., M. D. Boyle, B. A. Buttaro, M. Heinemann, and A. Podbielski. 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.
25. Kreikemeyer, B., K. S. McIver, and A. Podbielski. 2003. Virulence factor regulation and regulatory networks in Streptococcus pyogenes and their impact on pathogen-host interactions. Trends Microbiol. 11:224-232.
26. Lyon, W. R., C. M. Gibson, and M. G. Caparon. 1998. 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. 17:6263-6275.
27. Reference deleted.
28. Molinari, G., M. Rohde, S. R. Talay, G. S. Chhatwal, S. Beckert, and A. Podbielski. 2001. The role played by the group A streptococcal negative regulator Nra on bacterial interactions with epithelial cells. Mol. Microbiol. 40:99-114.
29. Musser, J. M., and F. R. DeLeo. 2005. Toward a genome-wide systems biology analysis of host-pathogen interactions in group A Streptococcus. Am. J. Pathol. 167:1461-1472.
30. Novick, R. P. 2003. Autoinduction and signal transduction in the regulation of staphylococcal virulence. Mol. Microbiol. 48:1429-1449.
31. Opdyke, J. A., J. R. Scott, and C. P. Moran. 2001. A secondary RNA polymerase sigma factor from Streptococcus pyogenes. Mol. Microbiol. 42:495-502.
32. Perez-Casal, J., M. G. Caparon, and J. R. Scott. 1991. Mry, a trans-acting positive regulator of the M protein gene of Streptococcus pyogenes with similarity to the receptor proteins of two-component regulatory systems. J. Bacteriol. 173:2617-2624.
33. Podbielski, A., M. Woischnik, B. A. Leonard, and K. H. Schmidt. 1999. Characterization of nra, a global negative regulator gene in group A streptococci. Mol. Microbiol. 31:1051-1064.
34. Ribardo, D. A., T. J. Lambert, and K. S. McIver. 2004. Role of Streptococcus pyogenes two-component response regulators in the temporal control of Mga and the Mga-regulated virulence gene emm. Infect. Immun. 72:3668-3673.
35. Ribardo, D. A., and K. S. McIver. 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.
36. Roberts, S. A., and J. R. Scott. 2007. RivR and the small RNA RivX: the missing links between the CovR regulatory cascade and the Mga regulon. Mol. Microbiol. 66:1506-1522.
37. Schrager, H. M., J. G. Rheinwald, and M. R. Wessels. 1996. Hyaluronic acid capsule and the role of streptococcal entry into keratinocytes in invasive skin infection. J. Clin. Investig. 98:1954-1958.
38. Shelburne, S. A., III, P. Sumby, I. Sitkiewicz, C. Granville, F. R. DeLeo, and J. M. Musser. 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. USA 102:16037-16042.
39. Sitkiewicz, I., and J. M. Musser. 2006. Expression microarray and mouse virulence analysis of four conserved two-component gene regulatory systems in group a streptococcus. Infect. Immun. 74:1339-1351.
40. Smoot, J. C., K. D. Barbian, J. J. Van Gompel, L. M. Smoot, M. S. Chaussee, G. L. Sylva, D. E. Sturdevant, S. M. Ricklefs, S. F. Porcella, L. D. Parkins, S. B. Beres, D. S. Campbell, T. M. Smith, Q. Zhang, V. Kapur, J. A. Daly, L. G. Veasy, and J. M. Musser. 2002. Genome sequence and comparative microarray analysis of serotype M18 group A streptococcus strains associated with acute rheumatic fever outbreaks. Proc. Natl. Acad. Sci. USA 99:4668-4673.
41. Sumby, P., K. D. Barbian, D. J. Gardner, A. R. Whitney, D. M. Welty, R. D. Long, J. R. Bailey, M. J. Parnell, N. P. Hoe, G. G. Adams, F. R. Deleo, and J. M. Musser. 2005. Extracellular deoxyribonuclease made by group A streptococcus assists pathogenesis by enhancing evasion of the innate immune response. Proc. Natl. Acad. Sci. USA 102:1679-1684.
42. 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. 2005. Evolutionary origin and emergence of a highly successful clone of serotype M1 group A streptococcus involved multiple horizontal gene transfer events. J. Infect. Dis. 192:771-782.
43. Sumby, P., A. R. Whitney, E. A. Graviss, F. R. DeLeo, and J. M. Musser. 2006. Genome-wide analysis of group a streptococci reveals a mutation that modulates global phenotype and disease specificity. PLoS Pathog. 2:e5.
44. Sung, K., S. A. Khan, M. S. Nawaz, and A. A. Khan. 2003. A simple and efficient Triton X-100 boiling and chloroform extraction method of RNA isolation from gram-positive and gram-negative bacteria. FEMS Microbiol. Lett. 229:97-101.
45. Suvorov, A. N., and J. J. Ferretti. 1996. Physical and genetic chromosomal map of an M type 1 strain of Streptococcus pyogenes. J. Bacteriol. 178:5546-5549.
46. Throup, J. P., K. K. Koretke, A. P. Bryant, K. A. Ingraham, A. F. Chalker, Y. Ge, A. Marra, N. G. Wallis, J. R. Brown, D. J. Holmes, M. Rosenberg, and M. K. Burnham. 2000. A genomic analysis of two-component signal transduction in Streptococcus pneumoniae. Mol. Microbiol. 35:566-576.
47. Vahling, C. M., and K. S. McIver. 2005. Identification of residues responsible for the defective virulence gene regulator Mga produced by a natural mutant of Streptococcus pyogenes. J. Bacteriol. 187:5955-5966.
48. Virtaneva, K., M. R. Graham, S. F. Porcella, N. P. Hoe, H. Su, E. A. Graviss, T. J. Gardner, J. E. Allison, W. J. Lemon, J. R. Bailey, M. J. Parnell, and J. M. Musser. 2003. Group A Streptococcus gene expression in humans and cynomolgus macaques with acute pharyngitis. Infect. Immun. 71:2199-2207.
49. Voyich, J. M., D. E. Sturdevant, K. R. Braughton, S. D. Kobayashi, B. Lei, K. Virtaneva, D. W. Dorward, J. M. Musser, and F. R. DeLeo. 2003. Genome-wide protective response used by group A streptococcus to evade destruction by human polymorphonuclear leukocytes. Proc. Natl. Acad. Sci. USA 100:1996-2001.
50. Walker, M. J., A. Hollands, M. L. Sanderson-Smith, J. N. Cole, J. K. Kirk, A. Henningham, J. D. McArthur, K. Dinkla, R. K. Aziz, R. G. Kansal, A. J. Simpson, J. T. Buchanan, G. S. Chhatwal, M. Kotb, and V. Nizet. 2007. DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection. Nat. Med. 13:981-985.