State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Changping, Beijing, China.
OIE Reference Lab for Swine Streptococcosis, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Virulence. 2022 Dec;13(1):1455-1470. doi: 10.1080/21505594.2022.2116160.
epidemic strains were responsible for two outbreaks in China and possessed increased pathogenicity which was featured prominently by inducing an excessive inflammatory response at the early phase of infection. To discover the critical genes responsible for the pathogenicity increase of epidemic strains, the genome-wide transcriptional profiles of epidemic strain SC84 were investigated at the early phase of interaction with BV2 cells. The overall low expression levels of 89K pathogenicity island (PAI) and 129 known virulence genes in the SC84 interaction groups indicated that its pathogenicity increase should be attributed to novel mechanisms. Using highly pathogenic strain P1/7 and intermediately pathogenic strain 89-1591 as controls, 11 pathogenicity increase crucial genes (PICGs) and 38 pathogenicity increase-related genes (PIRGs) were identified in the SC84 incubation groups. The PICGs encoded proteins related to the methionine biosynthesis/uptake pathway and played critical roles in the pathogenicity increase of epidemic strains. A high proportion of PIRGs encoded surface proteins related to host cell adherence and immune escape, which may be conducive to the pathogenicity increase of epidemic strains by rapidly initiating infection. The fact that none of PICGs and PIRGs belonged to epidemic strain-specific gene indicated that the pathogenicity increase of epidemic strain may be determined by the expression level of genes, rather than the presence of them. Our results deepened the understanding on the mechanism of the pathogenicity increase of epidemic strains and provided novel approaches to control the life-threatening infections of epidemic strains.
流行株引起了中国的两次暴发，其致病性增加，主要表现为在感染早期诱导过度炎症反应。为了发现导致流行株致病性增加的关键基因，我们研究了流行株 SC84 与 BV2 细胞相互作用早期的全基因组转录谱。在 SC84 相互作用组中，89K 致病性岛（PAI）和 129 个已知毒力基因的整体低表达水平表明，其致病性增加应该归因于新的机制。使用高致病性株 P1/7 和中度致病性株 89-1591 作为对照，在 SC84 孵育组中鉴定出 11 个致病性增加关键基因（PICGs）和 38 个致病性增加相关基因（PIRGs）。PICGs 编码与蛋氨酸生物合成/摄取途径相关的蛋白，在流行株致病性增加中发挥关键作用。大量 PIRGs 编码与宿主细胞黏附和免疫逃避相关的表面蛋白，这可能有利于流行株通过快速启动感染来增加其致病性。没有一个 PICGs 和 PIRGs 属于流行株特异性基因这一事实表明，流行株的致病性增加可能是由基因的表达水平决定的，而不是由它们的存在决定的。我们的研究结果加深了对 流行株致病性增加机制的理解，并为控制 流行株危及生命的感染提供了新的方法。
