Helen Marquis - Cornell Veterinary Medicine

Faculty

Hélčne Marquis

Associate Professor of Microbiology

Cornell University College of Veterinary Medicine
C5169 Veterinary Medical Center
E-mail: hm72@cornell.edu
Phone: 607-253-3273

DVM (University of Montreal)
PhD (Texas A&M University)

Dr. Marquis is an associate professor of Microbiology. She received a doctorate degree in Veterinary Medicine from the University of Montreal in Canada and was awarded a Ph.D. in Veterinary Microbiology from Texas A&M University for her studies on the outer membrane proteins of Brucella spp. with Dr. Thomas Ficht. She was a post-doctoral fellow in the laboratory of Dr. Daniel Portnoy at the University of Pennsylvania, working on the pathogenesis of Listeria monocytogenes. In 1997, she assumed a position of assistant professor in the Department of Microbiology at the University of Colorado School of Medicine. She moved to Cornell University in July 2001. Her research program is funded by the NIH.

Research Interests / Graduate Fields / Lab Members / Related Links / Selected References

Research Interests

The study of intracellular microbial pathogens allows a multidisciplinary approach to fundamental questions related to host cell/microbe interactions. My laboratory is studying the facultative intracellular Gram-positive bacterium L. monocytogenes. L. monocytogenes infects professional and non-professional phagocytic cells. Intracellular bacteria mediate vacuolar lysis, multiply in the host cytosol, and subvert the host humoral immune system by spreading from cell to cell without leaving the intracellular milieu. We are interested in two major areas of L. monocytogenes pathogenesis: (1) The mechanism controlling the compartmentalization and activation of a bacterial phospholipase C (PC-PLC), which contributes to bacterial escape from double membrane vacuoles; and (2) the regulation of L. monocytogenes pathogenesis by oxidative and nitrosative stress.

Hypothetical model of the regulation of PC-PLC translocation across the bacterial cell wall. The black crescent shape represents a putative chaperone that forms a stable complex with the proform of PC-PLC represented as an oval form with the propeptide as a cap. Upon a decrease in vacuolar pH, the complex comes apart and the propeptide is cleaved off. Both actions are Mpl-dependent. The uncomplexed form of PC-PLC is rapidly translocated across the cell wall.

Regulation of PC-PLC and Mpl activity. PC-PLC is made as a proenzyme whose activation requires proteolytic cleavage of a N-terminal propeptide. We showed that intracellular bacteria carry a pool of PC-PLC at the membrane-cell wall interface. Activation and secretion of bacteria-associated PC-PLC require a decrease in pH and Mpl, a metalloprotease of Listeria. Interestingly, like PC-PLC, Mpl is made as a proenzyme whose activation requires proteolytic cleavage of a N-terminal propeptide. Perhaps Mpl activation is the pH-regulated step in PC-PLC activation. We are interested in defining the mechanism(s) regulating PC-PLC compartmentalization and activation, and those regulating Mpl activity.

Regulation of L. monocytogenes pathogenesis by oxidative and nitrosative stress. Activated macrophages inhibit L. monocytogenes from escaping vacuoles, and this inhibition is due to the production of reactive oxygen and nitrogen oxide intermediates. We are investigating the susceptibility of bacterial factors that participate in vacuolar escape to modification and inactivation by these reactive radicals.

Graduate Fields

Dr. Marquis is a member of the following Graduate Fields:

Comparative Biomedical Sciences
Food Science and Technology
Microbiology

Lab Members

Alan Bitar, Lab Technical Support (apb33@cornell.edu)
Heather O'Neil, Graduate Student (hso2@cornell.edu)
Emily Slepkov, Postdoctoral Associate (ers44@cornell.edu)
Karthik Kota, Research Assistant (kk337@cornell.edu)
Brian Forster: Graduate Student (bmf34@cornell.edu)

Related Links

Program in Infection and Pathobiology (http://www.vet.cornell.edu/public/InfectionAndPathobiology/index.htm)

Graduate Program in Biological and Biomedical Sciences (http://www.vet.cornell.edu/OGE/BBMProgram/)

Seminars in Infection and Immunity: Fall, Spring

Bad Bug Book: Listeria monocytogenes (http://vm.cfsan.fda.gov/~mow/chap6.html)

Selected References

Snyder, A. and H. Marquis. (2003). Restricted translocation across the cell wall regulates secretion of the broad-range phospholipase C of Listeria monocytogenes. J. Bacteriol. 185:5953-5958.

Yeung, P.S.M., N. Zagorski, and H. Marquis. (2005). The metalloprotease of Listeria monocytogenes controls cell wall translocation of the broad-range phospholipase C. J. Bacteriol. 187:2601-2608.

O’Neil, H.S. and H. Marquis. (2006). Listeria monocytogenes flagella are used for motility, not as adhesins, to increase host cell invasion. Infect. Immun. 74:6675-6681.

Yeung, P.S.M., Y. Na, A.J. Kreuder, and H. Marquis. (2007). Compartmentalization of the broad-range phospholipase C activity to the spreading vacuole is critical for Listeria monocytogenes virulence. Infect. Immun. 75:44-51. This article was selected by the editors of Infection and Immunity for its significance to the field.

Cao, M., A. P. Bitar, and H. Marquis. (2007). A mariner-based transposition system for Listeria monocytogenes. Appl. Environ. Microbiol. 73:2758-2761.

Bitar, A.P., Cao, M., and H. Marquis. (2007). The metalloprotease of Listeria monocytogenes is activated by intramolecular autocatalysis. J. Bacteriol. (in press).

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Last Revised on October 22, 2007