Stony Brook University    |    School of Medicine
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Gloria Viboud

Phone: 631-444-3223

 

 

Research

Many bacterial pathogens cause disease by secreting molecules that enable them to evade the host's immune response. A specialized secretion machinery, the type III secretion system (TTSS), allows the bacteria to deliver virulence factors directly into the host cell. This system is widely distributed among a number of gram negative human pathogens that cause gastrointestinal diseases (Salmonella, Shigella, Vibrio, Yersinia), as well agents causing severe pneumonia, (Pseudomonas aeruginosa, Yersinia pestis), and sexually transmitted disease (Chlamydia).

TTSSs deliver effectors from the bacterial cytoplasm to the outer membrane through a secretion conduit. In turn, this channel is connected to a needle–like structure that transports the effectors directly into the host cell’s cytoplasm. Other proteins form a translocation channel at the plasma membrane through which the toxins are delivered into the host cell. One line of my research is aimed at understanding the molecular mechanisms of TTSS translocation in Yersinia. Our results support a new model in which the enteropathogen Yersinia pseudotuberculosis manipulates the host cell machinery to control effector translocation. This involves activation of the host cell Rho GTPase and actin polymerization by the interaction of components of the TTSS with the host cell membrane. We are currently investigating the mechanism by which components of the TTSS engage in signaling leading to Rho GTPase activation and actin polymerization, and most importantly, how this host cell changes control translocation. Studies that answer these questions should shed light on the molecular nature of the complex interaction between bacterial pathogens bearing TTSSs and the host cell. Importantly, components that act by modulating the TTSS are potential targets for novel antimicrobials.

Our second line of research deals with the role of a recently identified type III secretion system in the pathogenesis of non-toxigenic V. cholerae (NTVC). NTVC is a cause of waterborne diarrheal disease and extra-intestinal infection in developing nations. Whereas the pathogenesis of toxigenic V. cholerae has been extensively studied, the mechanism by which some members of the highly diverse group of NTVC cause disease remains unexplored. At least one effector protein, called VopF, is translocated by the TTSS in V. cholerae. A recent study shows that the TTSS is required for NTVC intestinal colonization in an infant mouse model. We envision that the presence of TTSS confers the ability to colonize the human intestine. To test our hypothesis, we are studying a group of 200 NTVC isolated from human and environmental samples in Argentina, and we are analyzing the prevalence of TTSS in theses strains. We are working to identify conditions that activate secretion of VopF in this group of NTVC, and we plan to search for additional proteins secreted in a TTSS-dependent manner. The opportunity to study a well-characterized and highly diverse collection of clinical and environmental NTVC, using a combination of epidemiology, molecular biology and proteomics offers a unique advantage to investigate the importance of the TTSS in the pathogenesis of NTVC. Importantly, these studies could lead to the development of new effective treatment for this, and other infections caused by TTSS-expressing bacteria. This is particularly relevant because diarrhea is one of the top preventable killers of children under five years old in developing countries.

Department of Molecular Genetics and Microbiology
Stony Brook University
Stony Brook, New York 11794-5222
Phone: 631-632-8800
Fax: 631-632-9797

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