Carbohydrate Availability Regulates Virulence Gene Expression in Streptococcus suis

Streptococcus suis is a major bacterial pathogen of young pigs causing worldwide economic problems for the pig industry. S. suis is also an emerging pathogen of humans. Colonization of porcine oropharynx by S. suis is considered to be a high risk factor for invasive disease. In the oropharyngeal cavity, where glucose is rapidly absorbed but dietary α-glucans persist, there is a profound effect of carbohydrate availability on the expression of virulence genes. Nineteen predicted or confirmed S. suis virulence genes that promote adhesion to and invasion of epithelial cells were expressed at higher levels when S. suis was supplied with the α-glucan starch/pullulan compared to glucose as the single carbon source. Additionally the production of suilysin, a toxin that damages epithelial cells, was increased more than ten-fold when glucose levels were low and S. suis was growing on pullulan. Based on biochemical, bioinformatics and in vitro and in vivo gene expression studies, we developed a biological model that postulates the effect of carbon catabolite repression on expression of virulence genes in the mucosa, organs and blood. This research increases our understanding of S. suis virulence mechanisms and has important implications for the design of future control strategies including the development of anti-infective strategies by modulating animal feed composition.猪链球菌（Streptococcus suis）是引发幼猪感染的主要细菌性致病菌，给全球养猪业造成了显著经济损失。同时，猪链球菌也是一类新发的人类致病菌。猪链球菌定植于猪口咽部，被认为是引发侵袭性疾病的高风险因素。在口咽腔环境中，葡萄糖可被快速吸收，但膳食来源的α-葡聚糖（α-glucans）仍会留存，碳水化合物的可获得性对毒力基因的表达具有显著调控作用。当以α-葡聚糖类物质淀粉/普鲁兰多糖（pullulan）作为单一碳源培养猪链球菌时，19个经预测或已证实的、可促进上皮细胞黏附与侵袭的猪链球菌毒力基因的表达水平显著升高。此外，当葡萄糖水平较低且猪链球菌以普鲁兰多糖为生长基质时，可损伤上皮细胞的毒素溶血素（suilysin）的产量提升了十余倍。基于生化、生物信息学以及体外与体内基因表达研究，我们构建了一套生物学模型，该模型阐释了碳分解代谢物阻遏（carbon catabolite repression）对黏膜、器官及血液中猪链球菌毒力基因表达的调控效应。本研究深化了我们对猪链球菌毒力作用机制的认知，同时为未来防控策略的制定提供了重要参考，包括通过调控动物饲料成分开发抗感染干预方案。