Olivia Ann Steele-Mortimer, Ph.D.

Senior Investigator

Salmonella Host-Cell Interations Section

NIAID/DIR

Building 6, Room 6212
903 S 4th Street
Hamilton, Mt 59840

406-363-9292

omortimer@niaid.nih.gov

Research Topics

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common cause of gastroenteritis in humans. Our group studies how S. Typhimurium interacts with mammalian cells. This facultative intracellular pathogen uses two type-three secretion systems (T3SS) to deliver bacterial effector proteins into the host cell. T3SS1 mediates invasion of nonphagocytic cells and early post-invasion events. In contrast, T3SS2 is induced following invasion and is required for survival and replication within the Salmonella-containing vacuole (SCV).

 

Scanning electron micrographs showing S. Typhimurium invading human intestinal epithelial cells (C2Bbe1).

Host Cell Proteins Involved in Invasion

T3SS1 is also known as the invasion-associated T3SS because it is essential for invasion of non-phagocytic cells. Multiple T3SS1 effector proteins target the actin cytoskeleton, directly or indirectly, to induce localized membrane ruffles on the cell surface. However, T3SS1 effectors are also important for early SCV biogenesis and other post-invasion processes. We are studying the role of the inositol phosphatase SopB, a T3SS1 effector that participates in invasion and early biogenesis of the SCV. In epithelial cells, SopB also stimulates phosphorylation and activation of the pro-survival kinase Akt via an indirect process that is not well understood. We are investigating the consequences of Akt activation in the context of Salmonella invasion, as this important kinase has many substrates and affects several essential cellular processes.

Biogenesis of the SCV

In epithelial cells, Salmonella can replicate within the membrane bound SCV or within the cytosol. Biogenesis of the SCV involves early interactions with the endocytic pathway followed by delivery of lysosomal membrane proteins and is dependent on both T3SS. We have used live cell imaging techniques to reveal the dynamic interactions that occur between the SCV and endosomes and lysosomes. More recently, we have used this same approach to investigate the bimodal lifestyle of intracellular Salmonella. These studies have shown that replication in the cytosol occurs more rapidly than in the SCV, at least in epithelial cells.

Biography

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. She came to the National Institutes of Health in 2001 and became a tenured senior investigator in 2007. Dr. Steele-Mortimer is an associate editor ofMicrobial Pathogenesis and is a member of the editorial board of Traffic.

Selected Publications

  1. Finn CE, Chong A, Cooper KG, Starr T, Steele-Mortimer O. A second wave of Salmonella T3SS1 activity prolongs the lifespan of infected epithelial cells. PLoS Pathog. 2017;13(4):e1006354.

  2. Jolly C, Winfree S, Hansen B, Steele-Mortimer O. The Annexin A2/p11 complex is required for efficient invasion of Salmonella Typhimurium in epithelial cells. Cell Microbiol. 2014;16(1):64-77.

  3. Knodler LA, Nair V, Steele-Mortimer O. Quantitative assessment of cytosolic Salmonella in epithelial cells. PLoS One. 2014;9(1):e84681.

  4. Bauler TJ, Starr T, Nagy TA, Sridhar S, Scott D, Winkler CW, Steele-Mortimer O, Detweiler CS, Peterson KE. Salmonella Meningitis Associated with Monocyte Infiltration in Mice. Am J Pathol. 2017;187(1):187-199.

  5. Lathrop SK, Binder KA, Starr T, Cooper KG, Chong A, Carmody AB, Steele-Mortimer O. Replication of Salmonella enterica Serovar Typhimurium in Human Monocyte-Derived Macrophages. Infect Immun. 2015;83(7):2661-71.


This page was last updated on August 4th, 2017