The bacterium Chlamydia trachomatis is the most commonly reported bacterial infection in the United States and the leading cause of sexually transmitted infections worldwide with approximately 90 million new cases reported annually. Infection by C. trachomatis can lead to severe medical complications in women including pelvic inflammatory disease; yet despite these concerns there are fundamental gaps in our understanding of Chlamydia pathogenesis, particularly with regards to the mechanisms used to manipulate host proteins for intracellular survival and dissemination. C. trachomatis is the first pathogen shown to usurp myosin phosphatase, a host protein that regulates myosin, during infection via the Chlamydial protein CT228. Myosin is an essential protein for many cellular process including muscle contraction, cell division, and the proliferation and migration of cancer cells. The long term goal of our research is to determine the role of myosin phosphatase and CT228 in C. trachomatis infection. Our central hypothesis based on our preliminary data is that the Chlamydial protein, CT228, is essential for myosin phosphatase recruitment and the extrusion method of host-cell exit in cell culture and a murine infection model. With developed of novel genetic tools and transformation methods, C. trachomatis is no longer genetically intractable and we propose to genetically complement and assess a CT228 deletion mutant and complemented strain in cell culture and murine infection model. These studies will determine the role of Chlamydial protein CT228 and myosin phosphatase with regards to Chlamydia pathogenesis and the extrusion method of host cell exit. As such, the proposed research is critical to understanding the role of myosin phosphatase during C. trachomatis infections and will address a key fundamental gap in Chlamydia pathogenesis. .

Public Health Relevance

Chlamydia trachomatis is a well-known sexually transmitted bacteria that causes millions of infections in the United States and worldwide yearly. This pathogen is very versatile and manipulates host proteins including myosin phosphatase which is required for many cell processes. This research will increase our knowledge on how this bacteria uses myosin during infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AI119906-01
Application #
8958528
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hiltke, Thomas J
Project Start
2015-07-01
Project End
2018-06-30
Budget Start
2015-07-01
Budget End
2018-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Oklahoma State University Stillwater
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
049987720
City
Stillwater
State
OK
Country
United States
Zip Code
74078
Shaw, Jennifer H; Behar, Amanda R; Snider, Timothy A et al. (2017) Comparison of Murine Cervicovaginal Infection by Chlamydial Strains: Identification of Extrusions Shed In vivo. Front Cell Infect Microbiol 7:18