Chlamydia trachomatis is a major cause of bacterial sexually transmitted infections. The regulation of gene expression in this important pathogen has not been well understood. Our long-range goals are to investigate the global regulatory mechanisms that allow C. trachomatis to survive in different conditions, as well as to persist in the host and contribute to human disease. We have demonstrated that the C. trachomatis alternative sigma factor, sigma 28, responds to heat shock and recognizes the hctB promoter of Chlamydia and also the fliC promoter of Escherichia coli. This suggests that sigma28 may be involved in transcription of a group of genes, which are required for an adaptation response enabling the successful completion of the developmental cycle. The objective of this proposal is to understand the biological function of one of the chlamydial sigma factors, sigma28, and to characterize its regulator(s). We propose two specific aims: 1) We will identify and characterize sigma28-dependent promoters and the sigma28 regulated target genes in C. trachomatis. We will also examine the activities of these promoters and their related target genes under conditions that are physiologically relevant for Chlamydia and 2) We will identify and characterize the putative regulator(s) of sigma28 in Chlamydia, and examine the effect on sigma28 specific transcription of interactions between sigma28 and its putative regulators. Information derived from these studies may lead to a better understanding of global regulation of genes, intracellular parasitism, virulence, immune evasion and persistence of C. trachomatis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI055869-05
Application #
7686508
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Hiltke, Thomas J
Project Start
2004-12-01
Project End
2009-11-30
Budget Start
2008-03-01
Budget End
2008-11-30
Support Year
5
Fiscal Year
2008
Total Cost
$252,000
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Type
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Shen, Li; Macnaughtan, Megan A; Frohlich, Kyla M et al. (2015) Multipart Chaperone-Effector Recognition in the Type III Secretion System of Chlamydia trachomatis. J Biol Chem 290:28141-55
Frohlich, Kyla; Hua, Ziyu; Wang, Jin et al. (2012) Isolation of Chlamydia trachomatis and membrane vesicles derived from host and bacteria. J Microbiol Methods 91:222-30
Wang, Jin; Frohlich, Kyla M; Buckner, Lyndsey et al. (2011) Altered protein secretion of Chlamydia trachomatis in persistently infected human endocervical epithelial cells. Microbiology 157:2759-71
Rao, Xiancai; Deighan, Padraig; Hua, Ziyu et al. (2009) A regulator from Chlamydia trachomatis modulates the activity of RNA polymerase through direct interaction with the beta subunit and the primary sigma subunit. Genes Dev 23:1818-29
Hua, Ziyu; Rao, Xiancai; Feng, Xiaogeng et al. (2009) Mutagenesis of region 4 of sigma 28 from Chlamydia trachomatis defines determinants for protein-protein and protein-DNA interactions. J Bacteriol 191:651-60
Shen, Li; Feng, Xiaogeng; Yuan, Yuan et al. (2006) Selective promoter recognition by chlamydial sigma28 holoenzyme. J Bacteriol 188:7364-77