Chlamydia trachomatis is a gram-negative bacterial pathogen that produces a host of major sexually transmitted diseases that result in serious reproductive morbidity. The organism is an obligate intracellular parasite with a complex and poorly understood development cycle involving the serial alternation of two morphologic forms. The goal of this project is to understand the genetic and molecular basis of this developmental cycle. We and others have previously characterized the cis acting signals involved in chlamydial gene expression. We now propose (i) to characterize the chlamydial RNA polymerase and to set up systems for the expression of chlamydial genes in vitro or in E. coli; (ii) to use these systems to further define chlamydial expression signals and the factors that regulate them; (iii) to identify developmentally regulated genes involved in the terminal stages of chlamydial differentiation during infection; and (iv) to develop methods for gene transfer into chlamydiae, to allow genetic dissection of the roles of chlamydial genes in the life cycle.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024436-06
Application #
3137424
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1988-02-01
Project End
1996-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kazmierczak, B I; Mostov, K; Engel, J N (2001) Interaction of bacterial pathogens with polarized epithelium. Annu Rev Microbiol 55:407-35
van Ooij, C; Kalman, L; van Ijzendoorn et al. (2000) Host cell-derived sphingolipids are required for the intracellular growth of Chlamydia trachomatis. Cell Microbiol 2:627-37
Stephens, R S; Fawaz, F S; Kennedy, K A et al. (2000) Eukaryotic cell uptake of heparin-coated microspheres: a model of host cell invasion by Chlamydia trachomatis. Infect Immun 68:1080-5
Van Ooij, C; Homola, E; Kincaid, E et al. (1998) Fusion of Chlamydia trachomatis-containing inclusions is inhibited at low temperatures and requires bacterial protein synthesis. Infect Immun 66:5364-71
Tan, M; Gaal, T; Gourse, R L et al. (1998) Mutational analysis of the Chlamydia trachomatis rRNA P1 promoter defines four regions important for transcription in vitro. J Bacteriol 180:2359-66
van Ooij, C; Apodaca, G; Engel, J (1997) Characterization of the Chlamydia trachomatis vacuole and its interaction with the host endocytic pathway in HeLa cells. Infect Immun 65:758-66
Fawaz, F S; van Ooij, C; Homola, E et al. (1997) Infection with Chlamydia trachomatis alters the tyrosine phosphorylation and/or localization of several host cell proteins including cortactin. Infect Immun 65:5301-8
Tan, M; Wong, B; Engel, J N (1996) Transcriptional organization and regulation of the dnaK and groE operons of Chlamydia trachomatis. J Bacteriol 178:6983-90
Tan, M; Engel, J N (1996) Identification of sequences necessary for transcription in vitro from the Chlamydia trachomatis rRNA P1 promoter. J Bacteriol 178:6975-82
Tan, M; Klein, R; Grant, R et al. (1993) Cloning and characterization of the RNA polymerase alpha-subunit operon of Chlamydia trachomatis. J Bacteriol 175:7150-9

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