Center for Infectious and Inflammatory Diseases
Member of the GSBS Faculty
Education and Post-Graduate Training
My lab is interested in the dynamic interactions between microbial pathogens and host. Research from our lab demonstrated that spores of Bacillus anthracis, a Gram-positive bacterium that causes anthrax, could adhere to and be taken up by a variety of host non-phagocytic cells including epithelial cells of the lung. We also showed that B. anthracis could cross an epithelial barrier without apparent damage to the barrier integrity, suggesting a transcellular route of translocation. Currently we are focusing on understanding the molecular details of how spores of B. anthracis are taken up by epithelial cells, how they breach the lung mucosal barrier, and how these processes affect disease progression and outcome. Specifically we aim to elucidate the components of intracellular signaling pathways that lead to the uptake of spores by epithelial cells, to map the intracellular route taken by the spores to pass through epithelial cells, and to examine these processes within the context of an infection using animal models. These studies fall into the general area of regulation of the actin cytoskeleton and vesicle trafficking. On the microbial side, we are interested in identifying the bacterial factors responsible for triggering the uptake and directing intracellular migration.
We employ a variety of approaches including molecular, biochemical, cellular, immunological, and genetic methods in our research. A tutorial in my laboratory would provide opportunities to learn concepts and techniques in the above areas.
Ponnuraj, K., Xu, Y., Moore, D., Deivanayagam, C. C., Boque, L., Höök, M., Narayana, S. V., 2002, ‘Crystallization and preliminary X-ray crystallographic analysis of Ace: a collagen-binding MSCRAMM from Enterococcus faecalis’, Biochim. Biophys. Acta. 1596: 173-6
Pikas, D. S., Brown, E. L, Gurusiddappa, S., Lee, L. Y., Xu, Y., Höök, M., 2003. ‘Decorin-binding sites in the adhesin DbpA from Borrelia burgdorferi: a synthetic peptide approach’, J. Biol. Chem., 278: 30920-6
Yi Xu, Jorge M. Rivas, Eric L. Brown, Xiaowen Liang, and Magnus Höök. 2004. ‘The virulence potential of the staphylococcal adhesin CNA in experimental arthritis is determined by its affinity for collagen’, J. Infect. Dis., 189:2323-2333.
Karthe Ponnuraj, M. Gabriela Bowden, Stacey Davis, S. Gurusiddappa, Dwight Moore, Damon Choe, Yi Xu, Magnus Höök, and Sthanam V. L. Narayana. 2003. ‘A “dock, lock, and latch” structural model for a Staphylococcal adhesin binding to fibrinogen’. Cell 115(2): 217-28.
Jouko Sillanpää, Yi Xu, Sreedhar R. Nallapareddy, Barbara E. Murray and Magnus Höök. ‘A family of putative MSCRAMMs from Enterococcus faecalis’. Microbiology, 2004, 150(Pt 7):2069-78.
Yi Xu, Xiaowen Liang, Yahua Chen, Theresa M. Koehler, and Magnus Höök. ‘Identification and biochemical characterization of two novel collagen binding MSCRAMMs of Bacillus anthracis’. J. Biol. Chem. 2004, 179 (50):51760-8.
Humtsoe JO, Kim JK, Xu Y, Keene DR, Höök M, Lukomski S, Wary KK. ‘A streptococcal collagen-like protein interacts with the alpha 2beta 1 integrin and induces intracellular signaling’. J. Biol. Chem. 2005, 280(14):13848-57.
Bowden MG, Chen W, Singvall J, Xu Y, Peacock SJ, Valtulina V, Speziale P, Höök M. ‘Identification and preliminary characterization of cell-wall-anchored proteins of Staphylococcus epidermidis’ Microbiology. 2005 May;151(Pt 5):1453-64.
Kim JK, Xu Y, Keene DR, Gurusiddappa S, Liang X, Wary KK, Höök M. ‘A novel binding site in collagen type III for the integrins, alpha 1beta 1 and alpha 2beta 1’ J Biol Chem. 2005, 280(37):32512-20
Yinong Zong, Yi Xu, Xiaowen Liang, Douglas R. Keene, Agneta Höök, S. Gurusiddappa, Magnus Höök, and Sthanam VL Narayana. ‘A “collagen hug” model for Staphylococcus aureus CNA binding to collagen’. EMBO J. 2005 Dec 21;24(24):4224-36.
Runlin Han, Antoni Zwiefka, Clayton C. Caswell, Yi Xu, Douglas R. Keene, Ewa Lukomska, Zhihong Zhao, Magus Hook, and Slawomir Lukomski. ‘Assessment of prokaryotic collagen-like sequences derived from streptococcal Scl1 and Scl2 proteins as a source of recombinant GXY polymers’. Appl. Microbiol. Biotechnol., 2006 March, 72(1):109-15.
Brooke H. Russell, Ranga Vasan, Douglas R. Keene, and Yi Xu. ‘Bacillus anthracis internalization by human fibroblasts and epithelial cells’. Cellular Microbiology. 2007, 9(5): 1262-1274
Brooke H. Russell, Ranga Vasan, Douglas R. Keene, Theresa M. Koehler, and Yi Xu. ‘Potential dissemination of Bacillus anthracis utilizing human lung epithelial cells’. Cellular Microbiology. Published online Dec 17, 2007.
For a complete list of publications, go to PubMed and enter xu y