Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that poses a serious threat to human health and the swine industry. The survival and travel in the bloodstream are the important causes for SS2, contributing to bacteremia, septicemia even septic shock. However, the related mechanism remains largely unknown. Preliminary experiment demonstrated that SS2 could largely attach to the surface of neutrophils, implying that this phenomenon maybe contributed to the travel of SS2 in bloodstream and then influenced its pathogenicity. To confirm this hypothesis, using a previously established screening method that combines affinity chromatography (based on liquid chromatography-tandem mass spectrometry) with shotgun proteomics, three candidate proteins (HP0487, HP1765, and HP1111) were identified from SS2 that could interact with neutrophils. Next, by constructing the deletion mutations, we demonstrated that HP0487 of three proteins could significantly influence the adhesion of SS2 to neutrophils. Furthermore, HP0487 was shown to contribute to the anti-phagocytosis of SS2 to neutrophils and RAW264.7 cells. More importantly, the deletion of HP0487 significantly reduced lethality and bacterial loads in vivo of SS2. Thus, our findings demonstrate that HP0487 contributes to SS2 virulence by mediating the adhesion and anti-phagocytosis of SS2 to neutrophils, promoting a better understanding about the pathogenesis of SS2.

猪链球菌血清型 2 (SS2) 是一种重要的人畜共患病原体，对人类健康和养猪业构成严重威胁。血流中的存活和传播是 SS2 的重要原因，导致菌血症、败血症甚至感染性休克。然而，相关机制在很大程度上仍然未知。初步实验表明，SS2 主要附着在中性粒细胞表面，表明这种现象可能有助于 SS2 在血流中的传播，进而影响其致病性。为了证实这一假设，使用先前建立的将亲和色谱（基于液相色谱-串联质谱）与鸟枪蛋白质组学相结合的筛选方法，从 SS2 中鉴定了三种可与中性粒细胞相互作用的候选蛋白质（HP0487、HP1765 和 HP1111）。下一个，通过构建缺失突变，我们证明了三种蛋白质的 HP0487 可以显着影响 SS2 对中性粒细胞的粘附。此外，HP0487 被证明有助于 SS2 对中性粒细胞和 RAW264.7 细胞的抗吞噬作用。更重要的是，HP0487 的缺失显着降低了致死率和细菌负荷体内SS2。因此，我们的研究结果表明，HP0487 通过介导 SS2 对中性粒细胞的粘附和抗吞噬作用来促进 SS2 毒力，促进对 SS2 发病机制的更好理解。