Key Lab of Animal Bacteriology of Ministry of Agriculture, College of Veterinary Medicine & OIE Swine Streptococcosis Diagnostic Laboratory, Nanjing Agricultural University, Nanjing 210095, China; Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China.
Key Lab of Animal Bacteriology of Ministry of Agriculture, College of Veterinary Medicine & OIE Swine Streptococcosis Diagnostic Laboratory, Nanjing Agricultural University, Nanjing 210095, China.
J Proteomics. 2018 May 30;180:41-52. doi: 10.1016/j.jprot.2017.12.001. Epub 2017 Dec 13.
Streptococcus suis (S. suis) is an emerging zoonotic agent that is responsible for significant economic losses to the porcine industry worldwide. However, most research regarding the pathogenic mechanisms has used in vitro cultures of S. suis, which may not provide an accurate representation of the in vivo biological activities. In this study, 188 differential abundance S. suis proteins were identified in in vivo samples obtained from the blood of the infected pigs. These were compared with in vitro samples by a Tandem Mass Tags (TMT) experiment. Thus, a virulence associated network was established using the enriched differential abundance proteins (obtained via bioinformatics analysis in this study) and the previously reported putative virulence factors associated with in vivo infection. One of the most important up-regulated hubs in this network, adhE (an acetaldehyde-CoA/alcohol dehydrogenase) was found. Furthermore, knocking out adhE in S. suis serotype 2 strain ZY05719 decreased virulence. Cell culture experiments and far-western blot analysis showed that adhE is involved in adhesion to Caco-2 cells; Hsp60 could be one of the receptors for this protein.
This study is a systematical research to identify in vivo regulated virulence associated proteins of S. suis in pigs. It constructs a network consisting of in vivo infection related factors for the first time to get to know the coordinated actions of a multitude of factors that lead to host pathogenicity and filter the most important hubs. The individual factors that contribute to infection is also identified. A novel differential protein adhE which is one of the most important hubs of this network and is up-regulated in abundance in vivo is found to moonlight as an important adhesion by binding Hsp60 and finally contributes to virulence.
猪链球菌（S. suis）是一种新兴的人畜共患病原体，它对全球养猪业造成了重大的经济损失。然而，大多数关于致病机制的研究都使用了猪链球菌的体外培养物，这可能无法准确反映体内的生物活性。在这项研究中，从感染猪的血液中获得了 188 个差异丰度的猪链球菌蛋白。通过串联质量标签（TMT）实验将这些蛋白与体外样本进行了比较。因此，使用本研究中通过生物信息学分析获得的富集差异丰度蛋白以及先前报道的与体内感染相关的假定毒力因子，建立了一个与毒力相关的网络。在这个网络中，最重要的上调枢纽之一是 adhE（乙醛-CoA/醇脱氢酶）。此外，在猪链球菌血清型 2 株 ZY05719 中敲除 adhE 降低了毒力。细胞培养实验和远西部印迹分析表明，adhE 参与了与 Caco-2 细胞的黏附；Hsp60 可能是该蛋白的受体之一。
本研究是一项系统研究，旨在鉴定猪体内猪链球菌的与毒力相关的差异调节蛋白。它首次构建了一个由体内感染相关因子组成的网络，以了解导致宿主致病性的多种因素的协调作用，并筛选出最重要的枢纽。还确定了导致感染的个别因素。发现一个新的差异蛋白 adhE 是这个网络中最重要的枢纽之一，在体内丰度上调，它作为一种重要的黏附因子，通过与 Hsp60 结合发挥作用，最终有助于毒力。
