Abstract

Streptococcus pyogenes, the group A streptococcus (GAS) is an important human pathogen causing frequent self-limiting diseases which may lead to serious sequelae. In addition, the GAS seems to be """"""""reemerging"""""""" as a cause of life-threatening invasive disease. Because of the great diversity of syndromes produced by many strains of GAS, we wish to improve our understanding of the pathogenesis of this organism by focusing on the regulation of expression of its genes, which presumably occurs on interaction with the human host to determine disease outcome. This proposal focuses on the two major global regulators that alter expression of many GAS proteins, including virulence factors. The regulation of expression of Mga (Aim 1) and CovR/S (CsrR/S) (Aim 3) will be studied. The genes controlled by Mga and CovR/S and the mechanisms by which these regulatory proteins control expression of these genes will also be investigated (Aims 2 and 4). We hope these analyses will improve our understanding at the molecular level of the interactions of GAS with its human host and may identify new targets for development of therapies and vaccines.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020723-23
Application #
7174763
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Rubin, Fran A
Project Start
1984-06-01
Project End
2008-09-10
Budget Start
2007-02-01
Budget End
2008-09-10
Support Year
23
Fiscal Year
2007
Total Cost
$396,897
Indirect Cost

  Institution

Name
Emory University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Bugrysheva, Julia V; Froehlich, Barbara J; Freiberg, Jeffrey A et al. (2011) The histone-like protein Hlp is essential for growth of Streptococcus pyogenes: comparison of genetic approaches to study essential genes. Appl Environ Microbiol 77:4422-8
Bugrysheva, Julia; Froehlich, Barbara J; Freiberg, Jeffrey A et al. (2011) Serine/threonine protein kinase Stk is required for virulence, stress response, and penicillin tolerance in Streptococcus pyogenes. Infect Immun 79:4201-9
Topp, Shana; Reynoso, Colleen M K; Seeliger, Jessica C et al. (2010) Synthetic riboswitches that induce gene expression in diverse bacterial species. Appl Environ Microbiol 76:7881-4
Churchward, Gordon; Bates, Christopher; Gusa, Asiya A et al. (2009) Regulation of streptokinase expression by CovR/S in Streptococcus pyogenes: CovR acts through a single high-affinity binding site. Microbiology 155:566-75
Froehlich, Barbara J; Bates, Christopher; Scott, June R (2009) Streptococcus pyogenes CovRS mediates growth in iron starvation and in the presence of the human cationic antimicrobial peptide LL-37. J Bacteriol 191:673-7
Barnett, Timothy C; Bugrysheva, Julia V; Scott, June R (2007) Role of mRNA stability in growth phase regulation of gene expression in the group A streptococcus. J Bacteriol 189:1866-73
Dalton, Tracy L; Collins, Julie T; Barnett, Timothy C et al. (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