Faculty
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Mary O’Riordan |
Host & Bacterial Adaptation to Intracellular Infection
Our research interests focus on the interaction between host cells and bacterial pathogens that live within the cell. We have recently found that macrophages, which are an important niche for many intracellular pathogens, can sense unique bacterial molecules within the cytosol. Triggering of this cytosolic surveillance pathway results in a characteristic pattern of gene expression that includes cytokines and other pro-inflammatory target genes. Using the Gram-positive intracytosolic bacterium, Listeria monocytogenes, as a model pathogen, we are identifying signaling molecules and transcriptional regulators that are specific to the cytosolic surveillance pathway.
In addition to studying the host response to cytosolic bacteria, we are investigating how bacteria can adapt to the specialized environment of the host cytosol. We have identified a bacterial gene involved in intermediary metabolism, lplA1, which is required for replication of Listeria monocytogenes only inside the host cell. This is strikingly reminiscent of recent studies showing that enzymes of the glyoxylate shunt pathway are important for pathogenesis of Mycobacterium tuberculosis and Candida albicans. We are working on identifying the function of lplA1 in Listeria pathogenesis and also finding other genes important in Listeria intracellular replication using a genetic approach.
Lastly, we are investigating the intracellular life cycle of Listeria monocytogenes in murine dendritic cells. Listeria can grow explosively in almost all cell types, but fails to grow in the cytosol of dendritic cells. Current studies are focused on identifying mechanisms by which dendritic cells can restrict the growth of intracellular pathogens.
Selected Publications:
Delbridge Bauler, C. Duckett and M. O’Riordan. XIAP regulates cytosolic-specific innate immunity to Listeria infection. PLoS Pathogens in press.
A. Radtke and M. O’Riordan. Homeostatic maintenance of pathogen-containing vacuoles requires TBK1-dependent regulation of aquaporin-1. Cellular Microbiology in press.
K. Keeney, J. Stuckey and M. O’Riordan. 2007. LplA1-dependent utilization of host lipoyl-peptides enables Listeria cytosolic growth and virulence. Molecular Microbiology. [Epub ahead of print]. Oct 1, 2007.
A. Radtke, L. Delbridge S. Balachandran, G. Barber and M. O’Riordan. 2007. TBK1 protects vacuolar integrity during intracellular bacterial infection. PLoS Pathogens. Mar 2;3(3):e29.
A. Radtke and M. O’Riordan. Innate resistance to intracellular bacterial pathogens. 2006. Cellular Microbiology. Nov;8(11):1720-9.
L. Delbridge and M. O’Riordan. Innate recognition of intracellular bacteria. Current Opinion in Immunology. 2006 Nov 23; [Epub ahead of print].
M. O’Riordan, M. A. Moors and D. A. Portnoy. 2003. Listeria intracellular growth and virulence require host-derived lipoic acid. Science. 302(5644): 462-4.
M. O’Riordan, C. H. Yi, R. Gonzales, K. D. Lee and D. A. Portnoy. 2002. Innate recognition of bacteria by a macrophage cytosolic surveillance pathway. Proc. Natl. Acad. Sci. 99(21): 13861-13866.
