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Abstract
Streptococcus suis is an important porcine bacterial pathogen and a zoonotic agent causing a variety of pathologies including sudden death, septic shock, and meningitis. Though serotype 2 is the most studied serotype due to its presence worldwide, serotype 9 is responsible for the greatest number of porcine cases in Spain, the Netherlands, and Germany. Regardless of its increasing importance, very few studies have investigated S. suis serotype 9 virulence factors and pathogenesis. Antigens I/II (AgI/II) are multimodal adhesion proteins implicated in host respiratory tract and oral cavity persistence of various pathogenic human streptococci. It was recently demonstrated that AgI/II is involved in various bacterial functions for serotype 9, participating in the initial steps of the pathogenesis of the infection. However, its contribution to the systemic infection remains unknown. As such, we evaluated herein the role of the S. suis serotype 9 AgI/II in the interactions with phagocytes and the development of systemic disease in a mouse model of infection. Results demonstrated that the presence of AgI/II is important for the development of clinical systemic disease by promoting bacterial survival in blood possibly due to its effect on S. suis phagocytosis, as shown with macrophages and dendritic cells. Furthermore, AgI/II directly participates in dendritic cell activation and pro-inflammatory mediator production following recognition by the Toll-like receptor pathway, which may contribute to the exacerbated systemic inflammation responsible for host death. Taken together, this study demonstrates that the S. suis serotype 9 AgI/II is important for virulence during systemic infection and development of disease. In fact, this is the first study to describe a role of an AgI/II family member in systemic bacterial disease.
Highlights
Streptococcus suis is a bacterial pathogen of post-weaning piglets responsible for important economic losses, with sudden death, meningitis, and arthritis being the most frequent clinical manifestations (Gottschalk et al, 2010)
Using C57BL/6 mice, which are routinely used as a model for serotype 2 virulence studies (Dominguez-Punaro et al, 2008; Lachance et al, 2013; Auger et al, 2016), the role of Antigens I/II (AgI/II) in S. suis serotype 9 systemic infection was evaluated following intraperitoneal inoculation
Mice infected with the complemented strain, C agI/II, presented similar clinical signs to those of mice infected with the wild-type strain, with 100% of mice succumbing to infection within the same time frame (Figure 1A)
Summary
Streptococcus suis is a bacterial pathogen of post-weaning piglets responsible for important economic losses, with sudden death, meningitis, and arthritis being the most frequent clinical manifestations (Gottschalk et al, 2010). Of the different described serotypes, serotype 2 is the most widespread and virulent (Goyette-Desjardins et al, 2014). Its prevalence in China (Zhu et al, 2011) and Canada (Gottschalk and Lacouture, 2015) has increased, with the first human case of S. suis serotype 9 infection reported in 2015 (Kerdsin et al, 2015). Regardless of its increasing importance, very few studies have investigated serotype 9 virulence factors and pathogenesis, with our understanding of the S. suis pathogenesis mostly based on serotype 2 studies (Wertheim et al, 2009; Fittipaldi et al, 2012; Segura et al, 2016). Certain factors have been proposed to be involved in serotype 9 survival, fitness, and persistence, as well as in host immune response interference, namely the LysM domain surface protein (Wu et al, 2016), a 5′ -nucleotidase (Dai et al, 2018), the XRE family transcription regulator SrtR (Hu et al, 2018), and the type VII secretion system putative substrate EsxA (Lai et al, 2017)
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