C. trachomatis variants have been described that are incapable of undergoing inclusion fusion in cell culture. These variants represent 1-2 percent of clinical isolates in Seattle and have been defined as lacking detectable IncA, a chlamydial protein that localizes to the inclusion membrane. Twenty-six independent incA mutant isolates have been sequenced and organized into several distinct categories. The overall goal of the proposed research is to identify distinctions between wild type and non-fusogenic strains and to exploit differences that are defined to better understand chlamydial development and pathogenesis. Experiments are planned to examine molecular and cell biology as well as clinical manifestations of the mutant chlamydiae. Each variant will be compared with matched wild-type controls. In the first aim molecular analyses will be done to determine mechanisms responsible for loss of expression of IncA and possibly other Inc's. In the second aim, growth and development of non-fusogenic strains will be studied in cell culture models. Finally, in the third aim the clinical relevance of the non-fusogenic phenotype will be determined using a retrospective case-control analysis and a monkey model of chlamydial infection. Study of these natural mutants will lead to a better understanding of chlamydial growth, development and pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI048769-01
Application #
6233486
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Savarese, Barbara M
Project Start
2001-03-01
Project End
2006-02-28
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
1
Fiscal Year
2001
Total Cost
$305,040
Indirect Cost
Name
Oregon State University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97339
Heinz, Eva; Rockey, Daniel D; Montanaro, Jacqueline et al. (2010) Inclusion membrane proteins of Protochlamydia amoebophila UWE25 reveal a conserved mechanism for host cell interaction among the Chlamydiae. J Bacteriol 192:5093-102
Alzhanov, Damir T; Weeks, Sara K; Burnett, Jeffrey R et al. (2009) Cytokinesis is blocked in mammalian cells transfected with Chlamydia trachomatis gene CT223. BMC Microbiol 9:2
Rockey, Daniel D; Wang, Jie; Lei, Lei et al. (2009) Chlamydia vaccine candidates and tools for chlamydial antigen discovery. Expert Rev Vaccines 8:1365-77
Suchland, R J; Sandoz, K M; Jeffrey, B M et al. (2009) Horizontal transfer of tetracycline resistance among Chlamydia spp. in vitro. Antimicrob Agents Chemother 53:4604-11
Chu, Hencelyn G; Weeks, Sara K; Gilligan, Diana M et al. (2008) Host alpha-adducin is redistributed and localized to the inclusion membrane in chlamydia- and chlamydophila-infected cells. Microbiology 154:3848-55
Suchland, Robert J; Jeffrey, Brendan M; Xia, Minsheng et al. (2008) Identification of concomitant infection with Chlamydia trachomatis IncA-negative mutant and wild-type strains by genomic, transcriptional, and biological characterizations. Infect Immun 76:5438-46
Alzhanov, Damir T; Suchland, Robert J; Bakke, Antony C et al. (2007) Clonal isolation of chlamydia-infected cells using flow cytometry. J Microbiol Methods 68:201-8
Xia, Minsheng; Suchland, Robert J; Bumgarner, Roger E et al. (2005) Chlamydia trachomatis variant with nonfusing inclusions: growth dynamic and host-cell transcriptional response. J Infect Dis 192:1229-36
Suchland, Robert J; Rockey, Daniel D; Weeks, Sara K et al. (2005) Development of secondary inclusions in cells infected by Chlamydia trachomatis. Infect Immun 73:3954-62
Alzhanov, Damir; Barnes, Jennifer; Hruby, Dennis E et al. (2004) Chlamydial development is blocked in host cells transfected with Chlamydophila caviae incA. BMC Microbiol 4:24

Showing the most recent 10 out of 19 publications