Yi Xu

Yi Xu

Associate Professor, Member of the GSBS Faculty

Center for Infectious and Inflammatory Diseases
2121 W. Holcombe Blvd.
Houston, TX   77030

Phone: 713-677-7570
Fax: 713-677-7576
yxu@ibt.tamhsc.edu

Education and Training

1998, Ph.D. in biochemistry and molecular biology - University of Texas Health Science Center at Houston

1998 – 2004, Postdoc, Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M, Houston, TX 

Research Interests

Bacteria and cancer; host-pathogen interactions; immune evasion.

Our lab is interested in the broad area of bacterial-host interactions. The manifestation and progression of infectious diseases are determined by the combined effects of bacterial factors and host reactions.  Understanding these interactions is critical for combating infectious diseases. Furthermore, some of the bacterial – host interactions may cause alterations in host physiological or cellular processes that contribute to other types of diseases including cancer. Currently there are two lines of research in the lab.

The role of bacteria in the development of cancer

It has been recognized that the gut microbiome has a profound influence in the health and disease status of the human body. Specific bacterial species or dysbiosis of the microbiome have been found to contribute to the development of colorectal cancer (CRC). This bacteria-CRC connection suggests a potential paradigm shift in the way CRC is detected, treated and managed. To realize this potential, a clear understanding of specific microbial components involved in the development of CRC and their mechanism of action is important. In our lab, we focus on Streptococcus gallolyticus subsp. gallolyticus (Sgg), previously known as S. bovis biotype I. This organism is known to strongly correlate with CRC. Patients with Sgg infections have elevated risks of developing colorectal adenoma/adenocarcinoma. Using a combination of cell cultures and mouse models, we recently demonstrated that Sgg actively promotes colon tumor growth. Analysis of tumor tissues and matched normal colon tissues from CRC patients further showed that the majority of tumor tissues are positive for Sgg and that Sgg preferentially associates with tumor tissues compared to normal tissues. These exciting discoveries highlight the importance of Sgg, as it not only has a strong clinical correlation with CRC but is also functionally important for the development of CRC. Our current focus is to understand the role of Sgg in the development of CRC in more specific details, and to elucidate the mechanisms underlying the tumor-promoting effect of Sgg.

Bacterial manipulation of the complement system.

The complement system is not only the first line of defense against microorganisms, but also links the innate immune system to the adaptive immune system. It is not surprising that manipulation of the complement system is a strategy adopted by several bacterial pathogens. We found that certain proteins on the surface of spores of Bacillus anthracis and other related organisms interact with components in the complement system. We are interested in understanding the molecular details of these interactions and how they affect the outcome of infections.

Selected Publications

Kumar, R., J. L. Herold, D. Schady, J. Davis, S. Kopetz, M. Martinez-Moczygemba, B. E. Murray, F. Han, Y. Li, E. Callaway, R. S. Chapkin, W. M. Dashwood, R. H. Dashwood, T. Berry, C. Mackenzie and Y. Xu (2017). "Streptococcus gallolyticus subsp. gallolyticus promotes colorectal tumor development." PLoS Pathog 13(7): e1006440.

Wang, Y., S. A. Jenkins, C. Gu, A. Shree, M. Martinez-Moczygemba, J. Herold, M. Botto, R. A. Wetsel and Y. Xu (2016). "Bacillus anthracis Spore Surface Protein BclA Mediates Complement Factor H Binding to Spores and Promotes Spore Persistence." PLoS Pathog 12(6): e1005678.

Jenkins SA and Xu Y. ‘Characterization of Bacillus anthracis persistence in vivo’. PLoS One, 2013 Jun 4;8(6):e66177.

Gu, C., Jenkins, S. A., Xue, Q., and Xu, Y. ‘Activation of the Classical Complement Pathway by Bacillus anthracis Is the Primary Mechanism for Spore Phagocytosis and Involves the Spore Surface Protein BclA’. J Immunol, 2012, 188(9):4421-31.

Qiong Xue, Chunfang Gu, Jose Rivera, Magnus Hook, Xiwu Chen, Ambra Pozzi, and Yi Xu. ‘Entry of Bacillus anthracis spores into epithelial cells is mediated by the spore surface protein BclA, integrin α2β1, and complement component C1q’. Cell Microbiol, 2011, 13(4): 620-34.

Qiong Xue, Sarah A. Jenkins, Chunfang Gu, Emanuel Smeds, Qing Liu, Ranga Vasan, Brooke Russell, and Yi Xu. ‘Bacillus anthracis spore entry into epithelial cells is an actin-dependent process requiring c-Src and PI3K’. PloS One. 2010, Jul 20; 5(7): e11665.

Scott E. Evans, Yi Xu, Michael J. Tuvim, and Burton F. Dickey. ‘Inducible Innate Resistance of Lung Epithelium to Infection’. Annu. Rev. Physiol. 2010, 72:413-435.

Brown EL, Xue Q, Jiang ZD, Xu Y, Dupont HL. ‘Pretreatment of epithelial cells with rifaximin alters bacterial attachment and internalization profiles.’ Antimicrob Agents Chemother. 2010 Jan;54(1):388-96.

Evans SE, Scott BL, Clement CG, Larson DT, Kontoyiannis D, Lewis RE, Lasala PR, Pawlik J, Peterson JW, Chopra AK, Klimpel G, Bowden G, Hook M, Xu Y, Tuvim MJ, Dickey BF. ‘Stimulated innate resistance of lung epithelium protects mice broadly against bacteria and fungi’. Am. J. Respir. Cell. Mol. Biol. 2010, 42: 40-50, PMID: 19329554.

Brooke H. Russell, Qing Liu, Sarah A. Jenkins, Michael J. Tuvim, Burton F. Dickey, and Yi Xu. ‘In vivo demonstration and quantification of intracellular Bacillus anthracis in lung epithelial cells’. Infect. Immun., 2008, 76(9): 3975-3983.

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. 2008, 10: 946-967.

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

Liu, Q., K. Ponnuraj, Y. Xu, V. K. Ganesh, J. Sillanpaa, B. E. Murray, S. V. Narayana and M. Hook (2007). "The Enterococcus faecalis MSCRAMM ACE Binds Its Ligand by the Collagen Hug Model." J Biol Chem 282(27): 19629-19637.

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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

Yi Xu, Douglas R. Keene, Janusz M. Bujnicki, Magnus Höök, and Slawomir Lukomski. 2002. ‘Streptococcal Scl1 and Scl2 proteins form collagen-like triple helices’. J. Biol. Chem. 277: 27312-27318.

Livia Visai, Yi Xu, Fabrizia Casolini, Simonetta Rindi, Magnus Höök and Pietro Speziale. 2000. ‘Monoclonal antibodies to CNA, a collagen-binding microbial surface component recognizing adhesive matrix molecules, detach Staphylococcys aureus from a collagen substrate’. J. Biol. Chem. 275: 39837-39845.

Yi Xu, Sivashankarappa Gurusiddappa, Rebecca L. Rich, Rick T. Owens, Douglas R. Keene, Richard Mayne, Agneta Höök, and Magnus Höök. 2000. ‘Multiple binding sites in collagen type I for the integrins alpha1beta1 and alpha2beta1’. J. Biol. Chem. 275: 38981-38989.

Yi Xu, Kavindra V. Singh, Xiang Qin, Barbara E. Murray, and George M. Weinstock. 2000. ‘Analysis of a gene cluster of Enterococcus faecalis involved in polysaccharide biosynthesis’. Infection and Immunity, 68: 815-823

Yi Xu, Barbara E. Murray, and George M. Weinstock. 1998. ‘A cluster of genes involved in polysaccharide biosynthesis from Enterococcus faecalis OG1RF’. Infection and Immunity, 66: 4313-4323.

Yi Xu, Lingxia Jiang, Barbara E. Murray, and George M. Weinstock. 1997. ‘Enterococcus faecalis antigens in human infections’. Infection and Immunity, 65: 4207-4215.