P12: Virulence gene regulation in the facultative intracellular pathogen Listeria monocytogenes, Y. Ananyina, Ed.Korenberg
Deputy Director for Science
Name of organization:
Gamaleya Research Institute for Epidemiology and Microbiology
Virulence gene regulation in the facultative intracellular pathogen Listeria monocytogenes
Background. Facultative intracellular pathogen Listeria monocytogenes has been in the focus of the research performed at the Department of Medical Microbiology of Gamaleya Research Institute for the last 15 years. The interest to this gram-positive bacterium arose in the late 80th all over the world with regard to recognizing it as a causative agent of serious, often fatal disease in humans and animals, listeriosis. Several outbreaks and many sporadic cases of listeriosis connected with consumption of food products contaminated with L. monocytogenes have been registered for the last 20 years with the mortality reached 20-30 %. A lot of research has been devoted to development of the methods for L. monocytogenes identification and differentiation in food products, as a major source of infection, and to study of the mechanisms that allow for this bacterium to penetrate and to multiply in eucaryotic host tissues that results in development of the disease. The major field of our interests is the fundamental research in the sphere of virulence gene regulation in L. monocytogenes and the mechanisms that allow bacteria to adapt to environmental conditions supplied by the host cell. The main results obtained by our group include the establishment of the autocrine mechanisms involved into L. monocytogenes virulence regulation (, and under preparation), the insight into environmental factors that affect virulence gene expression , establishment of the structural changes in a bacterial cell upon virulence regulon activation ; the study of structure-function relationships in the major virulence regulator protein PrfA ( and under preparation). The obtained results led to development of the essentially new method for L. monocytogenes identification ().
Summary. The ultimate goal of the proposed project is to get a comprehensive insight into the process of L. monocytogenes virulence gene regulation from the point of view of bacterial adaptation to environmental conditions inside the eucaryotic cell. Regulatory cascades that transduce environmental signals to the bacterial transcriptional machinery and control of virulence factor release will be under research. The special emphasis will be done on relations between general metabolic pathways and virulence factor regulation, and on the extended study of autocrine mechanisms that control virulence factor expression. The proposed research has the aim to reveal elements (signal molecule, receptor etc.) of the newly identified autocrine mechanism, which negatively controls virulence regulon, and its proposed relations with general cell metabolism; to establish the role of two-component signal transduction systems as the most likely candidates for the regulatory cascade connecting the extracellular space with transcriptional machinery. The main approach will include design and study of strains knock-out in genes recognized as targets on the base of the previous research or sequence similarity with established factors and their examination in vitro and on different cell culture types.
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