Laboratory of Intracellular Parasites
Olivia Steele-Mortimer, Ph.D.
Chief, Salmonella Host-Cell Interactions Section
Senior Investigator
Dr. Steele-Mortimer received her Ph.D. in cell biology from the European Molecular Biology Laboratory in 1994. From 1995 to 1999 she did postdoctoral research on Salmonella-Host cell interactions in the laboratory of B. Brett Finlay at the University of British Columbia in Vancouver followed by one year at Washington University, St Louis with Phillip D. Stahl. In 2001, she came to the NIH as a tenure-track investigator in the Laboratory of Intracellular Parasites and became a tenured Senior Investigator in 2007. Dr. Steele-Mortimer is a member of the editorial board of Traffic.
Description of Research Program
S. enterica serovar Typhimurium (S. Typhimurium) is a common cause of gastroenteritis in humans. Two type-three secretion systems (TTSS), which are essential for pathogenesis, are used to deliver bacterial effector proteins directly into the host cell. The Salmonella Pathogenicity Island 1 (SPI1)-encoded TTSS mediates invasion of nonphagocytic cells, while the SPI2-encoded TTSS is required for intracellular growth and survival. Once inside eukaryotic cells, S. enterica survive and replicate within salmonella-containing vacuoles (SCV).
Scanning electron micrographs showing S. Typhimurium invading human intestinal epithelial cells (C2Bbe1).
Major Areas of Research
Role of the SPI1 TTSS in post-invasion events
The SPI1 TTSS is also known as the invasion-associated TTSS because it is essential for invasion of nonphagocytic cells. However, it is now apparent that the expression and activity of SPI1 effectors are also important for SCV biogenesis and other post-invasion processes. We are studying the role of SopB/SigD, a SPI1 effector that participates in invasion but also has effects that can be detected several hours post invasion.
Sifs in salmonella-infected human epithelial cells (Hela). Intracellular salmonella (blue) translocate multiple effectors, including PipB (green), across the SCV membrane and into the host cell. Translocated effectors colocalize with lysosomal glycoproteins such as Lamp1 (red) on the Sif/SCV membranes.
Biogenesis of the SCV involves early interactions with the endocytic pathway followed by delivery of lysosomal membrane proteins and is dependent on both SPI1 and SPI2 TTSS. Replication of intracellular salmonella occurs after a lag of several hours post-invasion and is accompanied by the appearance of long membrane tubules (Sifs), which extend from the SCV. The exact nature of the SCV and Sifs and the mechanisms involved in their biogenesis remain unclear. We are using live cell imaging techniques to carry out extensive characterization of these compartments.
Function of the SPI2 effectors PipB and PipB2
Although the SPI2 TTSS was identified in the mid-1990s, remarkably little is known about the functions of individual SPI2 effectors. PipB and PipB2 have significant sequence homology and are both translocated into host cell membranes, where they are enriched in lipid rafts. However, the intracellular localizations only show partial overlap, and it appears that these two effectors have distinct roles. We are currently focusing on identifying the host cell targets of PipB and PipB2.
Research Group Members
Left to right: Leigh Knodler, Preeti Malik-Kale, Seth Winfree, Carrie Jolly, Antonio Ibarra Garcia, Monika Avello, Olivia Steele-Mortimer, Tarah OsowskiSelected Publications
(View list in PubMed.)
Knodler LA, Winfree S, Drecktrah D, Ireland R, Steele-Mortimer O. Ubiquitination of the bacterial inositol phosphatase, SopB, regulates its biological activity at the plasma membrane. Cell Microbiol. 2009 Nov;11(11):1652-70.
Drecktrah D, Levine-Wilkinson S, Dam T, Winfree S, Knodler LA, Schroer TA, Steele-Mortimer O. Dynamic behavior of Salmonella-induced membrane tubules in epithelial cells. Traffic. 2008 Dec;9(12):2117-29.
Drecktrah D, Knodler LA, Howe D, Steele-Mortimer O. Salmonella trafficking is defined by continuous dynamic interactions with the endolysosomal system. Traffic. 2007 Mar;8(3):212-25.
Drecktrah D, Knodler LA, Ireland R, Steele-Mortimer O. The mechanism of Salmonella entry determines the vacuolar environment and intracellular gene expression. Traffic. 2006 Jan;7(1):39-51.
Knodler LA, Bestor A, Ma C, Hansen-Wester I, Hensel M, Vallance BA, Steele-Mortimer O. Cloning vectors and fluorescent proteins can significantly inhibit Salmonella enterica virulence in both epithelial cells and macrophages: implications for bacterial pathogenesis studies. Infect Immun. 2005 Oct;73(10):7027-31.
Knodler LA, Steele-Mortimer O. The Salmonella effector PipB2 affects late endosome/lysosome distribution to mediate Sif extension. Mol Biol Cell. 2005 Sep;16(9):4108-23.
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