Abstract

The specific aims of this application will be to continue studies to define molecular and biochemical mechanisms involved in chlamydial-specific interactions with mammalian host cells.
The aims are derived from that demonstrated a novel and essential role for glycoaminoglycan-mediated chlamydial attachment and invasion of host cells. The hypothesis is that chlamydiae attach to host cells by a trimolecular complex in which heparin sulfate-like glycosaminoglycan bridges lectin like acceptors on chlamydia and heparin sulfate receptors on the mammalian host cell. This interaction elicits receptor mediated endocytosis of the infectious organisms. A molecular understanding of attachment and entry will provide a rational foundation for the study of other important microbiological characteristics such as inhibition of lysosomal fusion, EB-RB differentiation, and persistence of infection.
The specific aims are: 1) Molecular characterization of the glycosaminoglycan ligand (adhesin); 2) Characterize receptor-mediated endocytic pathway for host cell entry, 3) Identify and characterize the chlamydia glycosaminoglycan acceptor; and 4) Identify and characterize the mammalian host cell glycosaminoglycan receptor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI032943-07
Application #
2672134
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1992-07-01
Project End
2000-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Other Domestic Higher Education
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Abromaitis, Stephanie; Stephens, Richard S (2009) Attachment and entry of Chlamydia have distinct requirements for host protein disulfide isomerase. PLoS Pathog 5:e1000357
Abromaitis, Stephanie; Hefty, P Scott; Stephens, Richard S (2009) Chlamydia pneumoniae encodes a functional aromatic amino acid hydroxylase. FEMS Immunol Med Microbiol 55:196-205
Buchholz, Kerry R; Stephens, Richard S (2008) The cytosolic pattern recognition receptor NOD1 induces inflammatory interleukin-8 during Chlamydia trachomatis infection. Infect Immun 76:3150-5
Kleba, Betsy; Stephens, Richard S (2008) Chlamydial effector proteins localized to the host cell cytoplasmic compartment. Infect Immun 76:4842-50
Buchholz, Kerry R; Stephens, Richard S (2007) The extracellular signal-regulated kinase/mitogen-activated protein kinase pathway induces the inflammatory factor interleukin-8 following Chlamydia trachomatis infection. Infect Immun 75:5924-9
Conant, Carolyn G; Stephens, Richard S (2007) Chlamydia attachment to mammalian cells requires protein disulfide isomerase. Cell Microbiol 9:222-32
Hybiske, Kevin; Stephens, Richard S (2007) Mechanisms of Chlamydia trachomatis entry into nonphagocytic cells. Infect Immun 75:3925-34
Stephens, Richard S; Poteralski, Jesse M; Olinger, Lynn (2006) Interaction of Chlamydia trachomatis with mammalian cells is independent of host cell surface heparan sulfate glycosaminoglycans. Infect Immun 74:1795-9
Buchholz, Kerry R; Stephens, Richard S (2006) Activation of the host cell proinflammatory interleukin-8 response by Chlamydia trachomatis. Cell Microbiol 8:1768-79
Kleba, Betsy; Stephens, Richard S (2005) Bacteria-associated fibronectin does not enhance Chlamydia trachomatis infectivity in vitro. Microb Pathog 39:53-5

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