DESCRIPTION (provided by applicant): Chlamydia pneumoniae is a common human respiratory pathogen that has been associated with a variety of chronic diseases including atherosclerosis. C. pneumoniae, like other chlamydial species, is an obligate intracellular parasite that replicates within a vacuole, termed an inclusion. The inclusion membrane must serve numerous functions for the bacteria including regulating nutrient availability, evading fusion with host lysosomes, providing physical conditions to support replication, and transmitting signals that regulate the stages of chlamydial development. The inclusion membrane physically segregates bacteria from the host cytoplasm, yet it is actively modified by insertion of Chlamydia-derived proteins termed Incs (inclusion membrane proteins). Incs have been described most thoroughly in C. trachomatis where most are expressed shortly after chlamydiae enter a eukaryotic cell, raising the possibility that modification of the inclusion membrane is one of the first steps required for successful exploitation of a eukaryotic cell. A small number of Incs of C. trachomatis and C. psittaci have been previously identified and characterized; however, there is little known about the Incs of C. pneumoniae. Given their potential as host-interactive proteins, Incs represent an attractive target for elucidation of novel processes crucial to chlamydial pathogenesis. The typical Inc protein possesses a unique bilobed hydrophobic domain of approximately 40-80 amino acids. Using this unique hydrophobic domain as an indicator, numerous genes encoding Inc candidates can be identified in the genome of each chlamydial species. Many of the Inc proteins are common amongst all currently sequenced chlamydiae, yet there are also numerous predicted Inc proteins, which appear to be species-specific. The goals of this project are: i.) to identify and characterize C. pneumoniae-specific Incs that are localized to the chlamydial inclusion membrane and exposed to the host cytoplasm; ii.) to identify host cell proteins that interact with C. pneumoniae-specific Incs at the cytoplasmic face of the inclusion. Chlamydiae cause a range of diseases in humans that varies depending on the chlamydial species. Unlike the sexually transmitted disease caused by C. trachomatis, the respiratory pathogen C. pneumoniae is more common and infections can contribute to more serious complications such as cardiovascular disease. We propose to study proteins that are i) unique to C. pneumoniae and ii) directly interfere with normal functions within human cells.
|Effective start/end date||7/15/07 → 6/30/10|
- National Institutes of Health: $187,616.00
- National Institutes of Health: $218,900.00
- Immunology and Microbiology(all)