The projects described below are new initiatives that represent an effort to re-focus the Section's activities to emphasize molecular studies of more basic biological processes involved in prokaryotic intracellular parasitism. The current objective of these projects is defining the initial signal transducing event, G-proteins or tyrosine kinase, that may be coupled to the actual parasite receptor and exploring how these cellular regulatory cascades may modify the intracellular environment to benefit the parasite. Host cell responses to Chlamydia trachomatis infection detected so far include components of signal transduction pathways such as phospholipase C, phospholipase A2, and protein kinase C activities as well as calcium mobilization. One of the more dramatic examples of subversion of host constituents to effect a pathogenic mechanism is the mobilization of actin to promote intracellular movement and cell to cell spread of spotted fever group rickettsiae. Staining of Rickettsia rickettsii infected VERO cells with rhodamine phalloidin demonstrated unique actin filaments associated with one pole of intracellular rickettsiae. Biochemical evidence that actin polymerization plays a role in movement was provided by demonstrating that exocytosis of R. rickettsii from infected cells was inhibited by cytochalasin D. A recent finding of a histidine kinase-like gene related to prokaryotic two- component regulatory systems may provide some unique approaches toward identification of environmental signals that regulate specific genes intracellularly.
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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 |
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 |
Dautry-Varsat, Alice; Subtil, Agathe; Hackstadt, Ted (2005) Recent insights into the mechanisms of Chlamydia entry. Cell Microbiol 7:1714-22 |
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