Chlamydia trachomatis is the etiological agent of several significant diseases of humans including trachoma, the leading cause of infectious blindness worldwide. It is also the most common cause of sexually transmitted disease in the USA. Chlamydiae are obligate intracellular bacteria that undergo their life cycle entirely within an intracellular vesicle that is isolated from established routes of intracellular vesicle trafficking. Whereas the majority of intracellular parasites are thought to block maturation of the endocytic vesicle to a lysosome, chlamydiae dissociate themselves from this pathway and establish a functional interaction with an exocytic pathway which delivers sphingolipids from the Golgi apparatus to the plasma membrane. Interaction with this secretory pathway provides a novel pathogenic mechanism allowing chlamydiae to establish themselves in a site not destined to fuse with lysosomes. One of the initial events in chlamydial infection is the expression of a chlamydial gene product(s) that effectively isolates the inclusion from the endosomal/lysosomal pathway and initiates fusion competence with a subset of exocytic vesicles. Surprisingly, although chlamydiae intercept sphingolipids in transit to the plasma membrane, the processing and export of cellular glycoproteins is not inhibited. Thus chlamydiae interrupt a specific cellular pathway with minimal interference of normal cellular function. Collectively, the data suggest that the chlamydial inclusion occupies a site distal to the trans-Golgi apparatus with properties of an exocytic vesicle in which fusion with the plasma membrane is inhibited or delayed. These results show potential not only for defining the interactions of chlamydiae with the host cell but will serve as a model system for other obligate intracellular pathogens which occupy vacuoles that do not fuse with lysosomes. Understanding the initial events in chlamydial differentiation including the transition in properties of the endocytic vesicle to one which intersects an exocytic pathway remain significant challenges in understanding the pathogenic mechanisms of chlamydiae.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000567-08
Application #
6098971
Study Section
Special Emphasis Panel (LICP)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Mital, Jeffrey; Lutter, Erika I; Barger, Alexandra C et al. (2015) Chlamydia trachomatis inclusion membrane protein CT850 interacts with the dynein light chain DYNLT1 (Tctex1). Biochem Biophys Res Commun 462:165-70
Jewett, Travis J; Dooley, Cheryl A; Mead, David J et al. (2008) Chlamydia trachomatis tarp is phosphorylated by src family tyrosine kinases. Biochem Biophys Res Commun 371:339-44
Cocchiaro, Jordan L; Kumar, Yadunanda; Fischer, Elizabeth R et al. (2008) Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole. Proc Natl Acad Sci U S A 105:9379-84
Carabeo, Rey A; Dooley, Cheryl A; Grieshaber, Scott S et al. (2007) Rac interacts with Abi-1 and WAVE2 to promote an Arp2/3-dependent actin recruitment during chlamydial invasion. Cell Microbiol 9:2278-88
Grieshaber, Nicole A; Sager, Janet Burgess; Dooley, Cheryl A et al. (2006) Regulation of the Chlamydia trachomatis histone H1-like protein Hc2 is IspE dependent and IhtA independent. J Bacteriol 188:5289-92
Grieshaber, Scott S; Grieshaber, Nicole A; Miller, Natalie et al. (2006) Chlamydia trachomatis causes centrosomal defects resulting in chromosomal segregation abnormalities. Traffic 7:940-9
Grieshaber, Nicole A; Grieshaber, Scott S; Fischer, Elizabeth R et al. (2006) A small RNA inhibits translation of the histone-like protein Hc1 in Chlamydia trachomatis. Mol Microbiol 59:541-50
Fields, Kenneth A; Fischer, Elizabeth R; Mead, David J et al. (2005) Analysis of putative Chlamydia trachomatis chaperones Scc2 and Scc3 and their use in the identification of type III secretion substrates. J Bacteriol 187:6466-78
Clifton, Dawn R; Dooley, Cheryl A; Grieshaber, Scott S et al. (2005) Tyrosine phosphorylation of the chlamydial effector protein Tarp is species specific and not required for recruitment of actin. Infect Immun 73:3860-8
Wolf, Katerina; Fischer, Elizabeth; Hackstadt, Ted (2005) Degradation of Chlamydia pneumoniae by peripheral blood monocytic cells. Infect Immun 73:4560-70

Showing the most recent 10 out of 24 publications