The ultimate objective is to determine how chlamydiae are able to infect and colonize human mucosal epithelial cells. Chlamydial pathogenesis is characterized by a unique intracellular developmental cycle which is initiated when a single elementary body is endocytosed and terminates when infectious progeny is released into the environment upon cell death. The events preceding release and those preceding entry will be investigated. We will initially characterize two genetic loci which contain genes, called crp, encoding three distinct developmentally regulated cysteine-rich outer membrane proteins. The nucleotide sequence of each gene will be determined for three representative Chlamydia trachomatis serovars. The structure-function relationship of one of the crp gene products will be examined by utilizing a novel expression system which involves the 'exposition' of specific antigenic determinants at the surface of Escherichia coli. We will also examine the regulatory mechanism by analysis of crp-specific messenger RNA. The molecular mechanisms underlying endocytosis of the infectious elementary body will be studied by using a liposome reconstitution assay to identify adhesin(s) and an in vitro invasion assay to identify molecule(s) involved in entry. Substrates will include whole chlamydiae, purified chlamydial outer membrane proteins, and recombinants carrying exposed chlamydial virulence determinants. Chlamydial diseases are increasingly recognized as major health problems throughout the world. The identification and characterization of chlamydial genes encoding developmental products and virulence determinants will further the development of new reagents for the diagnosis, treatment and/or prevention of chlamydial infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026280-05
Application #
3140024
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1988-07-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1994-06-30
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Hsia, R C; Ting, L M; Bavoil, P M (2000) Microvirus of chlamydia psittaci strain guinea pig inclusion conjunctivitis: isolation and molecular characterization. Microbiology 146 ( Pt 7):1651-60
Bavoil, P M; Hsia, R; Ojcius, D M (2000) Closing in on Chlamydia and its intracellular bag of tricks. Microbiology 146 ( Pt 11):2723-31
Hsia, R; Ohayon, H; Gounon, P et al. (2000) Phage infection of the obligate intracellular bacterium, Chlamydia psittaci strain guinea pig inclusion conjunctivitis. Microbes Infect 2:761-72
Hsia, R C; Bavoil, P M (1996) Homologs of Escherichia coli recJ, gltX and of a putative 'early' gene of avian Chlamydia psittaci are located upstream of the 'late' omp2 locus of Chlamydia psittaci strain guinea pig inclusion conjunctivitis. Gene 176:163-9
Hsia, R C; Bavoil, P M (1996) Sequence analysis of the omp2 region of Chlamydia psittaci strain GPIC: structural and functional implications. Gene 176:155-62
Westbay, T D; Dascher, C C; Hsia, R C et al. (1995) Deviation of immune response to Chlamydia psittaci outer membrane protein in lipopolysaccharide-hyporesponsive mice. Infect Immun 63:1391-3
Ting, L M; Hsia, R C; Haidaris, C G et al. (1995) Interaction of outer envelope proteins of Chlamydia psittaci GPIC with the HeLa cell surface. Infect Immun 63:3600-8
Sinai, A P; Hayes, S F; Small, P L et al. (1995) Low-efficiency (macro-)pinocytic internalization of non-pathogenic Escherichia coli into HEp-2 cells. Res Microbiol 146:617-31
Westbay, T D; Dascher, C C; Hsia, R C et al. (1994) Dissociation of immune determinants of outer membrane proteins of Chlamydia psittaci strain guinea pig inclusion conjunctivitis. Infect Immun 62:5614-23
Dascher, C; Roll, D; Bavoil, P M (1993) Expression and translocation of the chlamydial major outer membrane protein in Escherichia coli. Microb Pathog 15:455-67

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