Studies on the pathogenesis of the infection caused by Streptococcus suis

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Streptococcus suis is one of the most economically important pathogens for the porcine industry, mainly causing sudden death and meningitis. Serotypes 2 and 9 are the most frequently isolated and virulent types worldwide. Virulence in S. suis is multifactorial and knowledge on the pathogenesis of the infection remains incomplete. The S. suis virulence factor studies published so far have been mainly performed with homogenous Eurasian serotype 2 strains that belong (as studied by multilocus sequence typing) to sequence type (ST)1. Most North American (NA) serotype 2 strains are genotypically/phenotypically very different from Eurasian strains, being either ST25 (virulent type) or ST28 (less virulent type). Also, little knowledge is available regarding serotype 9 virulence factors. Finally, clinical S. suis cases often occur in herds affected with concomitant viral infections such as the Porcine Swine Influenza Virus (SwIV) and the Reproductive and Respiratory Syndrome Virus (PRRSV). However, mechanisms underlying the synergy between these pathogens have not been studied. For the next 5 years, the short-term objectives of my research program are divided in two connected axes: 1. To further characterize virulence factors of S. suis: Firstly, we will characterize one putative virulence factor (antigen I/II), already identified in NA strains of S. suis serotypes 2 and 9, by obtaining mutants lacking this protein. Its role in persistence of the infection in the oral cavity and virulence will be evaluated. This objective will be followed by completely sequencing the DNA of virulent and low-virulent reference serotype 2 and 9 NA strains. Thereafter, the DNA of more than 100 field strains will be compared to that of the respective reference strains. Conserved genes present in virulent (but absent in low-virulent) strains will be identified and mutants lacking these factors will be obtained/characterized by testing their role using in vitro and in vivo tests. 2. To dissect bacterial-host interactions in the presence of viral co-infections: Firstly, we will complete our previous studies on the interactions of S. suis with SwIV-infected swine epithelial cells. In order to evaluate how viral infections affect the response against S. suis, immune cells such as porcine dendritic cells and pulmonary alveolar macrophages will be infected with either SwIV or PRRSV, and then co-infected with NA strains of S. suis to analyze cell responses including toxicity and cell death, capacity of immune cells to eliminate S. suis, and production of immune response mediators (cytokines). The possible role of virulence factors (objective 1) on viral co-infections will be also evaluated.  Past NSERC research helped us discover new insights on the S. suis infection. The research proposed for the next 5 years will consolidate the knowledge of our Canadian strains, allowing us to keep the international leadership on this subject.