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)
Brian Forster, Graduate student (bmf34@cornell.edu)
Karthik Kota, Research Assistant (kk337@cornell.edu)
Heather O'Neil, Graduate Student (hso2@cornell.edu)
Emily Slepkov, Postdoctoral Associate (ers44@cornell.edu)
Related Links
Program in Infection and Pathobiology
Graduate Program in Biological and Biomedical Sciences
Seminars in Infection and Immunity: Fall, Spring
Bad Bug Book: Listeria monocytogenes
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).
