Studies on the pathogenesis of the infections caused by streptococcus suis

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Streptococcus suis is one of the most important swine pathogens causing mainly septicemia, sudden death and meningitis. Serotype 2 and, to a lesser extent, serotype 14 are considered important emerging zoonotic agents and human cases have been described in Canada. Our understanding of the virulence factors and pathogenesis of S. suis infection has improved considerably in the last years but remains incomplete. Bacteria may enter via the tonsils or upper respiratory tract and disseminate in the bloodstream to cause septic shock through mechanisms related to an exacerbated inflammatory response. If the host survives, bacteria can reach the central nervous system, where they may induce a strong inflammatory response. This leads to an increase of leukocyte infiltration and intracranial pressure, causing the clinical signs of meningitis/encephalitis. The long-term objective of our research program is to better understand the interactions between Gram positive bacteria and host cells, thereby helping to advance the development of strategies for effective control of bacterial diseases, especially septic shock and meningitis. For the next five years we have three short-term objectives: 1. To further characterize S. suis virulence factors and their role in the pathogenesis of the infection, with specific studies on a) the sialic acid moiety of capsular polysaccharide; b) surface proteins, namely the protective surface protein SAO and the pili encoded by islands F and G; and c) resistance to killing by neutrophils in "neutrophils extracellular traps" as possibly conferred by encapsulation, D-alanylation of the LTA and secretion of enzymes with DNase and/or IL-8 serine protease activities; 2. To further delineate the interactions between S. suis and cells from the central nervous system, with emphasis on microglial cells and astrocytes; and 3. To study the receptors involved in inflammation leading to septic shock and meningitis, using our newly developed mouse model of infection. Financial support from NSERC will allow us to accomplish the objectives presented in this proposal, expand existing collaborations, develop new collaborations and maintain our internationally renowned research on this pathogen.