Institute for Microbiology, University of Veterinary Medicine, Hannover, Germany.
Department of Microbial Pathogenesis, Helmholtz Center for Infection Research, Braunschweig, Germany.
Microbiology (Reading). 2011 Jun;157(Pt 6):1823-1833. doi: 10.1099/mic.0.046417-0. Epub 2011 Feb 24.
Streptococcus suis is one of the most important pathogens in pigs and is also an emerging zoonotic agent. After crossing the epithelial barrier, S. suis causes bacteraemia, resulting in meningitis, endocarditis and bronchopneumonia. Since the host environment seems to be an important regulatory component for virulence, we related expression of virulence determinants of S. suis to glucose availability during growth and to the sugar metabolism regulator catabolite control protein A (CcpA). We found that expression of the virulence-associated genes arcB, representing arcABC operon expression, cps2A, representing capsular locus expression, as well as sly, ofs, sao and epf, differed significantly between exponential and early stationary growth of a highly virulent serotype 2 strain. Deletion of ccpA altered the expression of the surface-associated virulence factors arcB, sao and eno, as well as the two currently proven virulence factors in pigs, ofs and cps2A, in early exponential growth. Global expression analysis using a cDNA expression array revealed 259 differentially expressed genes in early exponential growth, of which 141 were more highly expressed in the CcpA mutant strain 10ΔccpA and 118 were expressed to a lower extent. Interestingly, among the latter genes, 18 could be related to capsule and cell wall synthesis. Correspondingly, electron microscopy characterization of strain 10ΔccpA revealed a markedly reduced thickness of the capsule. This phenotype correlated with enhanced binding to porcine plasma proteins and a reduced resistance to killing by porcine neutrophils. Taken together, our data demonstrate that CcpA has a significant effect on the capsule synthesis and virulence properties of S. suis.
猪链球菌是猪的最重要病原体之一，也是一种新兴的人畜共患病病原体。该菌穿过上皮屏障后引起菌血症，导致脑膜炎、心内膜炎和支气管肺炎。由于宿主环境似乎是毒力的重要调节成分，我们将猪链球菌的毒力决定因素的表达与生长过程中的葡萄糖可用性以及糖代谢调节剂分解代谢物控制蛋白 A (CcpA) 相关联。我们发现，毒力相关基因 arcB 的表达（代表 arcABC 操纵子的表达）、cps2A（代表荚膜基因座的表达）以及 sly、ofs、sao 和 epf 在高毒力血清型 2 菌株的指数生长和早期静止生长之间存在显著差异。ccpA 的缺失改变了表面相关毒力因子 arcB、sao 和 eno 的表达，以及在猪中已被证实的两种毒力因子 ofs 和 cps2A 在早期指数生长时的表达。使用 cDNA 表达谱的全局表达分析显示，早期指数生长时有 259 个差异表达基因，其中 141 个在 CcpA 突变株 10ΔccpA 中表达更高，而 118 个表达水平较低。有趣的是，在后者的基因中，有 18 个可以与荚膜和细胞壁合成有关。相应地，对菌株 10ΔccpA 的电子显微镜特征分析表明，其荚膜厚度明显减少。这种表型与增强对猪血浆蛋白的结合能力和降低对猪中性粒细胞杀伤的抵抗力相关。总之，我们的数据表明 CcpA 对猪链球菌的荚膜合成和毒力特性有显著影响。
