ZHAO-QING LUOAssociate Professor
Our laboratory is interested in understanding the cellular and molecular mechanisms that allow microbial pathogens to survive and multiply within the hostile host cells. We use Legionella pneumophila, the causative agent of Legionnaires disease as a model organism. This bacterium is a facultative intracellular pathogen capable of growing in a vacuole within macrophages as well as fresh water amoebae. After uptake, the Legionella-containing vacuole (LCV) in its early phase evades fusion with the lysosomal network and later is transformed into a compartment with characteristics of rough endoplasmic reticulum. Previous studies discovered that biogenesis of this replicative vacuole requires a Type IV protein secretion system termed Dot/Icm. Consisting of 26 proteins, the Dot/Icm system functions in injecting effector proteins into target host cells. Recently, by developing a genetic assay that allows us to directly monitor intercellular protein translocation, we have identified a large number of protein substrates transferred by the Dot/Icm complex. These virulence factors, designated Sid proteins are believed to directly interfere with host cellular functions to inhibit phagolysosomal fusion and to recruit ER- derived vesicles to the cytoplasmic surface of the LCV, thus allowing the establishment of the replicative compartment that supports bacterial growth. Our current focus is to analyze biochemical and cell biological activities conferred by these proteins and their roles in promoting the unique trafficking of the Legionella-containing vacuole in phagocytic cells. In particular, we are interested in identification of host proteins whose activities are modulated by substrates of the Dot/Icm system. The long term goal of these studies is to elucidate the molecular mechanisms underlying how this bacterium subverts host signal transduction pathways to establish a successful infection, such information will be invaluable in combating diseases caused by Legionella and other vacuolar pathogens.
Ph.D., University of Illinois at Urbana-Champaign, 2001
Professional Faculty Research
(Cellular microbiology) Type IV protein secretion of Legionella pneumophila; intracellular multiplication and trafficking of bacterial pathogens.
Hsu F, Zhu W, Brennan L, Tao L, Luo ZQ, Mao Y. 2012. Structure basis for substrate recognitionby a unique Legionella phosphoinositide phosphatase. Proc. Natl. Acad. Sci. USA. 109: 13567-72. PMID:22872863
Tan Y. Arnold A. J. and Luo Z.-Q. 2011. Legionella pneumophila regulates the small GTPase Rab1 activity by reversible phosphorylcholination. Proc. Natl. Acad. Sci. USA. 108:21212-7 PMID: 22158903
Tan Y. and Luo Z.-Q. 2011. Legionella pneumophila SidD is a deAMPylase that modifies Rab1. Nature. 475:506-509. PMID: 21734656
Fontana M. F. Banga S., Barry K. C., Shen X., Tan, Y., Luo Z.-Q*. and Vance E.V*. 2011. Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila. PLoS Pathogens . 7: e1001289. (*, co-corresponding authors)
Chen C.+, Banga S. +, Mertens K+., Weber M.M, Gorbaslieva I., Tan Y., Luo Z.-Q.* and Samuel J.E.* Large-scale identification and translocation of Type IV secretion substrates by Coxiella burnetii. 2010. Proc. Natl. Acad. Sci. USA. 107:21755-21760. (+, Co-first author, *, co-corresponding authors)
Xu L., Shen X., Bryan A., Banga S. Swanson M. and Luo ZQ. 2010. Inhibition of host vacuolar H+-ATPase activity by a Legionella pneumophila effector PLoS Pathogens. 6(3): e1000822. Epub 2010 Mar 19
Liu Y., Gao P., Banga S. and Luo Z.-Q. 2008. An in vivo gene deletion system for determining temporal requirement of bacterial virulence factors. Proc. Natl. Acad. Sci. USA. 105:9385-9390.
Banga S., Gao, P., Shen X., Fiscus V., Zong W-X., Chen L. and Luo Z.-Q. 2007. Legionella pneumophila inhibits macrophage apoptosis by targeting pro-death members of the Bcl2 protein family. Proc. Natl. Acad. Sci. USA. 104:5121-5126