The Host-Parasite Interactions Section studies the basic molecular and cellular biology of chlamydiae and other obligate intracellular parasites. 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 United States.
Chlamydiae are obligate intracellular bacteria with a biphasic developmental cycle that involves cell types adapted for extracellular survival and intracellular multiplication. This developmental cycle consists of an environmentally stable cell form, termed the elementary body (EB), and a functionally and morphologically distinct vegetative cell type, termed the reticulate body (RB). Chlamydiae undergo their developmental cycle entirely within a parasitophorous vacuole, termed an inclusion, that is isolated from established routes of endocytic vesicle trafficking. Whereas the majority of intracellular parasites are thought to block maturation of the endocytic vesicle to a lysosome, chlamydiae rapidly dissociate themselves from this pathway and establish a functional interaction with an exocytic pathway that delivers sphingolipids and cholesterol from the Golgi apparatus to the plasma membrane. Interaction with this secretory pathway is thought to constitute a novel pathogenic mechanism whereby chlamydiae establish themselves in a site not destined to 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, remains a significant challenge in deciphering the pathogenic mechanisms of chlamydiae. A number of scientific approaches are integrated in studies of early differentiation and subversion of host functions. These include global regulation of chlamydial gene expression via histone-like proteins, vesicular trafficking, cytoskeletal interactions, cell signaling, chlamydial modification of the inclusion membrane, and interactions mediated by Type III secreted protein effectors, which control entry and subsequent events.
Rickettsia rickettsii is a member of the spotted fever group rickettsiae and the etiologic agent of Rocky Mountain spotted fever (RMSF). R. rickettsii is a small, obligate, intracellular, Gram-negative organism maintained in its tick host through transovarial transmission. Infection with R. rickettsii occurs through the bite of an infected tick. Once the organism gains access to the host, it is able to replicate within the host vascular endothelial cells and spread from cell to cell by polymerizing host cell actin. If not diagnosed and treated properly, infection with R. rickettsii results in a severe and potentially life threatening disease, although strains of R. rickettsii vary dramatically in their virulence in animal model systems and severity of human disease. The focus of efforts here is understanding the molecular mechanisms involved in the pathogenesis of RMSF.
With the completed sequences of multiple rickettsial species and recently developed technologies to genetically manipulate rickettsiae, it has become possible to investigate differences between virulent and avirulent strains of rickettsiae through comparative genomics and molecular biology.
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Dr. Hackstadt received his Ph.D. from Washington State University. His postdoctoral work was in the NIAID Laboratory of Microbial Structure and Function. Dr. Hackstadt then assumed an associate professorship in the departments of pathology and microbiology at the University of Texas Medical School in Galveston. In 1990, he returned to NIAID, where he was appointed chief of the Host-Parasite Interactions Section, awarded tenure in 1995, and appointed to the National Institutes of Health Senior Biomedical Research Service in 2005. He currently serves on the editorial boards of Traffic, Cellular Microbiology, and Infection and Immunity. He is a past president of the American Society for Rickettsiology and was elected a fellow of the American Academy of Microbiology in 2005.
Pictured left to right: Laura Bauler, Dave Mead, Anders Omsland, Alex Barger, Nick Noriea, Ted Hackstadt, DeAnna Bublitz, Cheryl Dooley, Tina Clark, Janet Sager, Erika Lutter.
Bauler LD, Hackstadt T. Expression and targeting of secreted proteins from Chlamydia trachomatis. J Bacteriol. 2014 Apr;196(7):1325-34.
Lutter EI, Barger AC, Nair V, Hackstadt T. Chlamydia trachomatis inclusion membrane protein CT228 recruits elements of the myosin phosphatase pathway to regulate release mechanisms.Cell Rep. 2013 Jun 27;3(6):1921-31.
Mital J, Miller NJ, Dorward DW, Dooley CA, Hackstadt T. Role for chlamydial inclusion membrane proteins in inclusion membrane structure and biogenesis.PLoS One. 2013 May 17;8(5):e63426.
Omsland A, Sager J, Nair V, Sturdevant DE, Hackstadt T. Developmental stage-specific metabolic and transcriptional activity of Chlamydia trachomatis in an axenic medium. Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19781-5.
Mital J, Hackstadt T. Diverse requirements for SRC-family tyrosine kinases distinguish chlamydial species. MBio. 2011 Mar 22;2(2). pii: e00031-11.
Kleba B, Clark TR, Lutter EI, Ellison DW, Hackstadt T. Disruption of the Rickettsia rickettsii Sca2 autotransporter inhibits actin-based motility.Infect Immun. 2010 May;78(5):2240-7.
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Last Updated July 01, 2015