Studies on the pathogenesis of the infections caused by Streptococcus suis

牲畜抗菌剂使用量的减少和疫苗的缺乏导致了导致养猪业重大经济损失的细菌病原体的重新出现。其中包括引起北美断奶仔猪严重系统性疾病的猪链球菌，由于需要干预工具和减少抗菌剂的使用，猪链球菌被认为是养猪业最优先考虑的细菌之一。总共描述了29个血清型，其中2型被认为是最重要的，特别是在欧亚大陆(EA)。然而，NA的情况似乎不同，除了血清2型，其他血清型(例如，血清1/2)也占主导地位，尽管它们的毒力因素尚不清楚。此外，猪链球菌2型NA株的表型/基因特征与EA株不同：它们起源于不同的祖先，具有不同的毒力潜力，可能通过不同的致病机制诱导疾病。事实上，几乎所有已发表的关于这种血清型的研究都是在EA菌株上进行的。此外，毒力菌株的存在并不总是保证疾病的发展，辅助因素是重要的贡献者。例如，饲料中真菌毒素(如脱氧雪腐镰刀菌烯醇)的存在可能会影响动物的肠道上皮细胞通透性和/或先天免疫反应，增加它们对猪链球菌感染的易感性。这项计划的长期目标是扩大关于猪链球菌感染发病机制的基础知识，包括导致疾病的辅助因素。我们对这一建议的一般假设是，NA毒株的毒力因子与EA毒株的毒力因子不同，此外，农场的辅助因子对疾病的发展有重要贡献。在我们专业知识的基础上，未来五年的两个主要目标是：1)确定和表征猪链球菌未描述的和保守的毒力因素；2)评估霉菌毒素(更具体地说是脱氧雪腐镰刀菌烯醇)作为与猪链球菌相关疾病发展的辅助因素的作用。不同的分子方法和体外/体内研究将有助于阐明与NA毒力和致病机制有关的特定因素。霉菌毒素在肠道和全身水平的作用(以及涉及的机制)也将在体外和体内进行评估。本项目将对猪链球菌NA毒株的特性提供新的见解，揭示新的毒力因子和致病机制。用真菌毒素获得的结果可能进一步揭示导致疾病发展的重要辅助因素。针对这种主要病原体的疫苗的未来开发和其他减轻疾病发展风险的战略对养猪业至关重要，因为它旨在减少抗菌剂的使用。

The reduction in livestock antimicrobial use and lack of vaccines led to the re-emergence of bacterial pathogens responsible for significant economic loss in the swine industry. Among them is Streptococcus suis, which causes serious systemic diseases in weened piglets in North America (NA) and is considered as one of the bacterial species of highest priority in the swine industry based on the need for intervention tools and the reduction of antimicrobial use. A total of 29 serotypes have been described, and serotype 2 is considered by far the most important, especially in Eurasia (EA). However, the situation in NA seems to be different and, in addition to serotype 2, other serotypes (e.g., serotype 1/2) are also predominant, although their virulence factors are unknown. Moreover, S. suis serorype 2 NA strains phenotypically/genotypically different from EA strains: they originate from different ancestors, possess different virulence potential and probably induce disease through different pathogenicity mechanisms. Indeed, almost all published studies on this serotype have been carried out on EA strains. Also, the presence of virulent strains does not always guarantee the development of disease, and co-factors are significant contributors. For example, the presence of mycotoxins in feed (such as deoxynivalenol) may affect intestinal epithelial cell permeability and/or the innate immune response of animals, increasing their susceptibility to S. suis infection. The long-term objective of this program is to expand fundamental knowledge on the pathogenesis of S. suis infections, including co-factors contributing to the disease. Our general hypothesis for this proposal is that virulence factors of NA strains differ from those of EA strains and, in addition, co-factors at the farm significantly contribute to the development of disease. Building on our expertise, the two main objectives over the next five years are to: 1) identify and characterize undescribed and conserved virulence factors of NA S. suis strains; 2) evaluate the role of mycotoxins (more specifically deoxynivalenol) as a co-factor in the development of S. suis-associated diseases. Different molecular methods and in-vitro/in vivo studies will help elucidate specific factors involved in the virulence and pathogenesis of the infection caused by NA strains. The effect of mycotoxins (and the mechanisms involved) at the intestinal and systemic levels will also be evaluated in vitro and in vivo. This program will provide new insights into the specific characteristics of NA strains of S. suis, revealing new virulence factors and mechanisms of pathogenicity. Results obtained with mycotoxins may further uncover important co-factors leading to the development of disease. The future development of a vaccine against this major pathogen and other strategies to mitigate risks of disease development are of utmost significance to the swine industry as it aims to reduce antimicrobial use.