Chlamydia trachomatis is an intracellular bacterium that is a major cause of sexually transmitted diseases and infectious blindness. Chlamydia's survival largely relies on two fundamental processes 1) protecting its infectious intracellular compartment (so-called inclusion) from the lysosomal degradative pathway and 2) hijacking host compartments to acquire nutrients and material necessary to grow the inclusion. To perform both these events, C. trachomatis evolved to be extraordinarily efficient at manipulating membrane fusion and promote its survival. Despite the importance of this intimate connection between Chlamydia and host vesicular trafficking, very little is known regarding the impact of this bacterium on the host membrane fusion machinery, the so-called SNAREs. Do Chlamydiae extensively co-opt SNAREs to control the host vesicular trafficking and promote their survival inside the cell? Using an innovative multidisciplinary approach, we seek to determine whether C. trachomatis (i) uses multiple SNARE-like proteins to sequentially block different host SNARE complexes involved in the endocytic/lysosomal pathway and protect its inclusion from destruction and (ii) recruits host SNAREs involved in the secretory pathway to hijack host vesicles and promote the growth of its inclusion. The characterization of multiple chlamydial SNARE-like proteins will give scientists the fundamental tools to screen for their presence in the proteome of other major human pathogens, including Salmonella typhi, and Mycobacterium tuberculosis, thus opening new avenues of research.

Public Health Relevance

Chlamydia trachomatis infections remain one of the most prevalent bacterial sexually transmitted diseases, and despite the availability of antibiotics, the number of infections has been increasing since the 1980s. Understanding how Chlamydia establishes a successful intracellular lifestyle after it invades host cells will facilitate the development of novel drugs that specifically target its pathogenic mechanisms. In particular, determining how Chlamydia co-opts host vesicular trafficking will provide powerful therapeutic opportunities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56AI073486-05A1
Application #
8904883
Study Section
Host Interactions with Bacterial Pathogens Study Section (HIBP)
Program Officer
Hiltke, Thomas J
Project Start
2009-07-01
Project End
2015-07-31
Budget Start
2014-08-19
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
$387,500
Indirect Cost
$137,500
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107