Members of the genus Chlamydia, a group of obligate intracellular procaryotic pathogens, are important causes of human infectious diseases. Chlamydia pneumoniae recently has been implicated in the initiation and development of atherosclerosis. Chlamydia trachomatis is a major cause of preventable infectious blindness and the leading cause of bacterial sexually transmitted diseases (STD). Upper genital tract complications in females represents a significant women's health issue. Silent pelvic inflammatory disease (PID) can lead to tubal obstructive infertility. This serious disease will require extensive investigation to understand the pathogenic processes that cause irreparable damage of the reproductive tract in women during their child-bearing years. It is important to discern pathologic changes that accompany atherosclerosis, trachoma, PID and tubal obstructive disease as these events actually occur in infected people, but studies involving human populations do not lend themselves well to carefully controlled experimental conditions. Therefore we propose to continue our work using a variety of cell culture systems (human and murine) to study general features of persistent intracellular chlamydial growth which may be common to all chronic chlamydial infections and pursue the murine-C. trachomatis genital tract in vivo model to study the hypothesis that persistent chlamydiae may contribute to the development of upper genital tract disease. This hypothesis will be tested by building on our experience related to the effects of immune response regulated cytokines on chlamydial host cell activation that results in enhanced expression of chlamydial stress response proteins together with new information on the effects of stress response proteins on the disease process. We also will study how these fundamental events in the basic biology of chlamydiae relate to chronic disease as exemplified by upper genital tract infections in mice. The work plan will comprise 4 specific aims, 2 of which are intended to broaden our cell culture knowledge of persistent (stressed) chlamydial growth and 2 of which will apply this knowledge to an in vivo system. Results will lead to increased information concerning how the basic biology of chlamydiae directly impacts the disease process and the development of chronic chlamydial disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019782-15
Application #
6328671
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Quackenbush, Robert L
Project Start
1982-08-01
Project End
2004-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
15
Fiscal Year
2001
Total Cost
$257,980
Indirect Cost
Name
University of Wisconsin Madison
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Grayston, J Thomas; Belland, Robert J; Byrne, Gerald I et al. (2015) Infection with Chlamydia pneumoniae as a cause of coronary heart disease: the hypothesis is still untested. Pathog Dis 73:1-9
Peters, Jan; Byrne, Gerald I (2015) Chlamydia trachomatis growth depends on eukaryotic cholesterol esterification and is affected by Acyl-CoA:cholesterol acyltransferase inhibition. Pathog Dis 73:ftv028
Patil, Renukadevi; Szabó, Erzsébet; Fells, James I et al. (2015) Combined mitigation of the gastrointestinal and hematopoietic acute radiation syndromes by an LPA2 receptor-specific nonlipid agonist. Chem Biol 22:206-16
Bonner, Carol A; Byrne, Gerald I; Jensen, Roy A (2014) Chlamydia exploit the mammalian tryptophan-depletion defense strategy as a counter-defensive cue to trigger a survival state of persistence. Front Cell Infect Microbiol 4:17
Bavoil, Patrik M; Byrne, Gerald I (2014) Analysis of CPAF mutants: new functions, new questions (the ins and outs of a chlamydial protease). Pathog Dis 71:287-91
Abdelsamed, Hossam; Peters, Jan; Byrne, Gerald I (2013) Genetic variation in Chlamydia trachomatis and their hosts: impact on disease severity and tissue tropism. Future Microbiol 8:1129-1146
Jonsson, Colleen B; Cole, Kelly Stefano; Roy, Chad J et al. (2013) Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents. J Bioterror Biodef Suppl 3:12634
Miyairi, Isao; Ziebarth, Jesse; Laxton, Jonathan D et al. (2012) Host genetics and Chlamydia disease: prediction and validation of disease severity mechanisms. PLoS One 7:e33781
Ziebarth, Jesse D; Bhattacharya, Anindya; Chen, Anlong et al. (2012) PolymiRTS Database 2.0: linking polymorphisms in microRNA target sites with human diseases and complex traits. Nucleic Acids Res 40:D216-21
Peters, Jan; Onguri, Vijaya; Nishimoto, Satoru K et al. (2012) The Chlamydia trachomatis CT149 protein exhibits esterase activity in vitro and catalyzes cholesteryl ester hydrolysis when expressed in HeLa cells. Microbes Infect 14:1196-204

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