ABSTRACT

The Streptococcus suis serotype 2 (SS2) is a significant zoonotic pathogen that is responsible for various swine diseases, even causing cytokine storms of Streptococcal toxic shock-like syndromes amongst human. Cell wall anchoring proteins with a C-terminal LPxTG are considered to play vital roles during SS2 infection; however, their exporting mechanism across cytoplasmic membranes has remained vague. This study found that YSIRK-G/S was involved in the exportation of LPxTG-anchoring virulence factors MRP and SspA in virulent SS2 strain ZY05719. The whole-genome analysis indicated that diverse LPxTG proteins fused with an N-terminal YSIRK-G/S motif are encoded in strain ZY05719. Two novel LPxTG proteins SspB and YzpA were verified to be exported via a putative transport system that was dependent on the YSIRK-G/S directed translocation, and portrayed vital functions during the infection of SS2 strain ZY05719. Instead of exhibiting an inactivation of C5a peptidase in SspB, another LPxTG protein with an N-terminal YSIRK-G/S motif from Streptococcus agalactiae was depicted to cleave the C5a component of the host complement. The consequent domain-architecture retrieval determined more than 10,000 SspB/YzpA like proteins that are extensively distributed in the Gram-positive bacteria, and most of them harbor diverse glycosyl hydrolase or peptidase domains within their middle regions, thus presenting their capability to interact with host cells. The said findings provide compelling evidence that LPxTG proteins with an N-terminal YSIRK-G/S motif are polymorphic effectors secreted by Gram-positive bacteria, which can be further proposed to define as cell wall anchoring effectors in a new subset.

摘要

该猪链球菌血清型 2 (SS2) 是一种重要的人畜共患病病原体，可导致多种猪病，甚至引起人类链球菌中毒性休克样综合征的细胞因子风暴。具有 C 端 LPxTG 的细胞壁锚定蛋白被认为在 SS2 感染过程中起着至关重要的作用；然而，它们跨细胞质膜的输出机制仍然模糊不清。本研究发现，YSIRK-G/S 参与了毒力 SS2 菌株 ZY05719 中 LPxTG 锚定毒力因子 MRP 和 SspA 的输出。全基因组分析表明，与 N 端 YSIRK-G/S 基序融合的多种 LPxTG 蛋白在菌株 ZY05719 中编码。两种新型 LPxTG 蛋白 SspB 和 YzpA 经证实可通过依赖于 YSIRK-G/S 定向易位的假定转运系统输出，并描绘了 SS2 菌株 ZY05719 感染期间的重要功能。与 SspB 中 C5a 肽酶失活不同，另一种具有 N 端 YSIRK-G/S 基序的 LPxTG 蛋白来自无乳链球菌被描述为切割宿主补体的 C5a 成分。随后的域结构检索确定了 10,000 多个 SspB/YzpA 样蛋白，它们广泛分布在革兰氏阳性菌中，其中大多数在其中间区域具有不同的糖基水解酶或肽酶域，从而展示了它们与宿主相互作用的能力细胞。上述发现提供了令人信服的证据，证明具有 N 端 YSIRK-G/S 基序的 LPxTG 蛋白是革兰氏阳性细菌分泌的多态效应子，可以进一步提出将其定义为新子集中的细胞壁锚定效应子。