Studies on the pathogenesis of the infections caused by Streptococcus suis

猪链球菌感染发病机制的研究

• 批准号: RGPIN-2022-03730
• 负责人: Gottschalk, Marcelo
• 金额: $ 3.42万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=743397
• 关键词: Studies; pathogenesis; infections; caused; Streptococcus

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.

牲畜抗菌药物使用的减少和疫苗的缺乏导致细菌病原体重新出现，造成养猪业的重大经济损失。其中包括猪链球菌，它会在北美 (NA) 的断奶仔猪中引起严重的全身性疾病，并且基于对干预工具的需求和抗菌药物使用的减少，被认为是养猪业中最优先考虑的细菌物种之一。总共描述了 29 种血清型，其中 2 型血清型被认为是迄今为止最重要的，尤其是在欧亚大陆 (EA)。然而，NA 的情况似乎有所不同，除了血清型 2 外，其他血清型（例如血清型 1/2）也占主导地位，尽管其毒力因子未知。此外，猪链球菌血清2 NA菌株在表型/基因型上与EA菌株不同：它们起源于不同的祖先，具有不同的毒力潜力，并且可能通过不同的致病机制诱发疾病。事实上，几乎所有已发表的关于该血清型的研究都是针对 EA 菌株进行的。此外，强毒株的存在并不总是保证疾病的发展，辅助因素是重要的促成因素。例如，饲料中霉菌毒素（如脱氧雪腐镰刀菌烯醇）的存在可能会影响动物的肠上皮细胞通透性和/或先天免疫反应，增加其对猪链球菌感染的易感性。该计划的长期目标是扩大有关猪链球菌感染发病机制的基础知识，包括导致该疾病的辅助因素。我们对此提议的一般假设是，NA 菌株的毒力因子与 EA 菌株的毒力因子不同，此外，农场的辅助因子对疾病的发展有显着影响。基于我们的专业知识，未来五年的两个主要目标是：1）识别和表征猪纳链球菌菌株未描述和保守的毒力因子； 2) 评估霉菌毒素（更具体地说是脱氧雪腐镰刀菌烯醇）作为猪链球菌相关疾病发展中的辅助因子的作用。不同的分子方法和体外/体内研究将有助于阐明与 NA 菌株引起的感染的毒力和发病机制有关的特定因素。霉菌毒素（及其相关机制）在肠道和全身水平的影响也将在体外和体内进行评估。 该计划将为猪链球菌NA菌株的具体特征提供新的见解，揭示新的毒力因子和致病机制。用霉菌毒素获得的结果可能会进一步揭示导致疾病发生的重要辅助因素。针对这种主要病原体的疫苗的未来开发以及降低疾病发展风险的其他策略对养猪业至关重要，因为它的目标是减少抗菌药物的使用。