Helen Marquis - Cornell Veterinary Medicine

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.

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 Listeria monocytogenes. L. monocytogenes is a food-borne pathogen that affects primarily immunodeficient individuals, pregnant women, and a large variety of vertebrate animals. Following invasion in the intestinal tract, the bacterium has a predilection for the liver, the CNS, and the gravid uterus, resulting in high levels of mortality. During infection, L. monocytogenes resides in the cytosol of infected cells and subvert the host humoral immune system by spreading from cell to cell without leaving the intracellular milieu. We are presently pursuing three projects in the lab: (1) Mechanisms controlling the compartmentalization and activity of pro-enzymes contributing to bacterial escape from vacuoles; (2) Modulation of innate immunity by a bacterial phospholipase; and (3) Development of a L. monocytogenes-based vaccine for cutaneous leishmaniasis.

Regulation of PC-PLC and Mpl activity. The broad-range phospholipase C of L. monocytogenes (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. Mpl is made as a proenzyme whose activation occurs by autocatalysis. Similar to PC-PLC, the compartmentalization of Mpl is regulated by its propeptide and by pH. We are interested in defining at the molecular and biochemical levels the mechanism(s) regulating the compartmentalization and activation of PC-PLC and Mpl.

The role of PC-PLC in modulating the innate immune response to infection. A mutant of L. monocytogenes that has lost the ability to regulate PC-PLC activity is strongly attenuated in the mouse. We are testing the hypothesis that constitutive secretion of active PC-PLC in infected cells hastens and enhances the innate immune response to infection.

Listeria-based vaccine for cutaneous leishmaniasis. In this project, we are using L. monocytogenes to deliver sandfly salivary gland antigens in the cytosol of infected cells, aiming at the development of a robust and long-lasting protection against cutaneous leishmaniasis.

Bitar, A.P., M. Cao, and H. Marquis. 2008. The metalloprotease of Listeria monocytogenes is activated by intramolecular autocatalysis. J. Bacteriol. 190:107-111.

O’Neil, H.S., B.M. Forster, K.L. Roberts, A.J. Chambers, A.P. Bitar, and H. Marquis. 2009. The propeptide of the metalloprotease of Listeria monocytogenes controls compartmentalization of the zymogen during intracellular infection. J. Bacteriol. 191:3594-3603.

Zemansky, J., B.C. Kline, J.J. Woodward, J.H. Leber, H. Marquis, and D.A. Portnoy. 2009. Development of a mariner-based transposon and identification of Listeria monocytogenes determinants, including the peptidyl-prolyl isomerase PrsA2, that contribute to its hemolytic activity. J. Bacteriol. 191:3950-3964.

Xayarath, B., H. Marquis, G. C. Port, and N. E. Freitag. 2009. Listeria monocytogenes CtaP is a multifunctional cysteine transport-associated protein required for bacterial pathogenesis. Mol Microbiol. 74:956-973.

Slepkov, E.R., A. Pavinski Bitar, and H. Marquis. 2010. Differentiation of propeptide residues regulating the compartmentalization, maturation and activity of the broad-range phospholipase C of Listeria monocytogenes. Biochem. J. 432:557-563.