Scott S. Grieshaber, Ph.D.
- Research Fellow, Rocky Mountain Labs, NIAID, NIH
- Ph.D., University of Wyoming
- B.S., Microbiology, Colorado State University
Chlamydia trachomatis is the most common cause of sexually transmitted disease (STD) in developed countries and the most frequent cause of preventable blindness worldwide. Other species of medical importance include C. pneumonia an agent of upper respiratory tract infections and of current interest due to a possible association with atherosclerosis, and C. psittaci, which is primarily a pathogen of animals but occasionally is transmitted to humans.
Chlamydia spp. are obligate intracellular bacteria with a unique developmental cycle that takes place entirely within a membrane bound parasitophorous vacuole termed an inclusion. Two morphologically distinct forms characterize the chlamydial developmental cycle; elementary bodies (EBs) are the extracellular infectious form, and reticulate bodies (RBs) are the intracellular replicative form. Our goals are to study the interface between Chlamydia and the host cell, identifying the mechanisms by which chlamydia creates its intracellular niche and how this impacts cells at both an invitro and invivo level.
Our current research focuses on understanding and describing the unique mechanism by which C. trachomatis hijacks the microtubule system during infection and how this interaction effects the host. Within 2 hr after entry into host cells, C. trachomatis EBs are trafficked to the perinuclear region of the host cell and remain in close proximity to the Golgi apparatus. This migration requires chlamydial protein synthesis and is dependent on host cell microtubules. We have been able to show that chlamydial migration resembles host cell vesicular trafficking. The Chlamydiae move toward the minus end of the microtubules and aggregate at the microtubule-organizing center (MTOC). We are currently in the process of dissecting the molecular mechanisms of this trafficking. In mammalian cells the major minus end directed microtubule motor is cytoplasmic dynein. We have shown that microinjection of antibodies to a subunit of cytoplasmic dynein inhibits movement of Chlamydiae to the MTOC. We are currently in the process of further characterizing this process as well as identifying those chlamydial factors controlling it.
Migration of the inclusion is a unidirectional process resulting in the chlamydial inclusion remaining in a juxtanuclear location associated with the MTOC of the host cell. The microtubule network is organized at the MTOC by centrosomes, which coordinate cellular architecture during interphase as well as the bipolar spindles for DNA segregation during mitosis Defects in centrosomes have been implicated as a mechanism leading to cancer; thus, the strong interaction of the chlamydial inclusion with dynein may prove to be a potential mechanism for the increased rate of cancer formation in patients with a past chlamydial infection. Indeed, we have recently found that the interaction between the chlamydial inclusion and the centrosome leads to a significant increase in supernumerary centrosomes, abnormal spindle poles and chromosomal segregation defects; thus leading to chromosome instability. The potential differences between the host and chlamydial activation of dynein will be an attractive target for control of chlamydial infections and mitigation of its potential transforming function.
- Grieshaber S. S., Grieshaber N. A., Miller N., Hackstadt T. 2006. Chlamydia trachomatis Causes Centrosomal Defects Resulting in Chromosomal Segregation Abnormalities. Traffic, 7:
- Grieshaber NA, Grieshaber SS, Fischer ER, Hackstadt T. 2006. A small RNA inhibits translation of the histone-like protein Hc1 in Chlamydia trachomatis. Mol Microbiol. 59:541-550.
- Clifton, D., C. A. Dooley, S. S. Grieshaber, R. A. Carabeo, K. A. Fields, T. Hackstadt. 2005. Tyrosine phosphorylation of chlamydial Tarp is species specific and not required for the recruitment of actin. Infect Immun. 73:3860-3868.
- Carabeo, R. A., S. S. Grieshaber, C. A. Dooley, A. Hasenkrug, and T. Hackstadt. 2004. Requirement for the Rac GTPase in Chlamydia trachomatis Invasion of Non-Phagocytic Cells. Traffic, 5:418-425.
- Clifton, D., K. A. Fields, S. S. Grieshaber, D. Mead, C. A. Dooley, R. A. Carabeo, and T. Hackstadt. 2004. Chlamydia trachomatis ct456 is a translocated and tyrosine phophoylated protein that recruits actin to the site of entry. PNAS, Jul 6;101(27):10166-71.
- Grieshaber, S. S., N. A. Grieshaber, and T. Hackstadt. 2003. Chlamydia trachomatis uses host cell dynein to traffic to the microtubule-organizing center in a p50 dynamitin-independent process. J Cell Sci. 116:3793-3802.
- Harlander, R. S., M. Way, Q. Ren, D. Howe, S. S. Grieshaber, and R. A. Heinzen. 2003. Effects of ectopically expressed neuronal Wiskott-Aldrich syndrome protein domains on Rickettsia rickettsii actin-based motility. Infect Immun. 71:1551-1556.
- Grieshaber, S., J. A. Swanson, and T. Hackstadt. 2002. Determination of the physical environment within the Chlamydia trachomatis inclusion using ion-selective ratiometric probes. Cell Microbiol. 4:273-283.
- Carabeo, R. A., S. S. Grieshaber, E. Fischer, and T. Hackstadt. 2002. Chlamydia trachomatis induces remodeling of the actin cytoskeleton during attachment and entry into HeLa cells. Infect Immun. 70:3793-3803.
- Grieshaber, S. S., D. H. Lankenau, T. Talbot, S. Holland, and N. S. Petersen. 2001. Expression of the 53 kD forked protein rescues F-actin bundle formation and mutant bristle phenotypes in Drosophila. Cell Motil Cytoskeleton. 50:198-206.
- Grieshaber, S. S., and N. S. Petersen. 1999. The Drosophila forked protein induces the formation of actin fiber bundles in vertebrate cells. J Cell Sci. 112:2203-2211.
- Heinzen, R. A., S. S. Grieshaber, K. Van, L. S., and C. J. Devin. 1999. Dynamics of actin-based movement by Rickettsia rickettsii in vero cells. Infect Immun. 67:4201-4207.