PDF(Pubmed)
Abstract：
The evolutionary conserved YopJ family comprises numerous type-III-secretion system (T3SS) effectors of diverse mammalian and plant pathogens that acetylate host proteins to dampen immune responses. Acetylation is mediated by a central acetyltransferase domain that is flanked by conserved regulatory sequences, while a nonconserved N-terminal extension encodes the T3SS-specific translocation signal. Bartonella spp. are facultative-intracellular pathogens causing intraerythrocytic bacteremia in their mammalian reservoirs and diverse disease manifestations in incidentally infected humans. Bartonellae do not encode a T3SS, but most species possess a type-IV-secretion system (T4SS) to translocate Bartonella effector proteins (Beps) into host cells. Here we report that the YopJ homologs present in Bartonellae species represent genuine T4SS effectors. Like YopJ family T3SS effectors of mammalian pathogens, the \"Bartonella YopJ-like effector A\" (ByeA) of Bartonella taylorii also targets MAP kinase signaling to dampen proinflammatory responses, however, translocation depends on a functional T4SS. A split NanoLuc luciferase-based translocation assay identified sequences required for T4SS-dependent translocation in conserved regulatory regions at the C-terminus and proximal to the N-terminus of ByeA. The T3SS effectors YopP from Yersinia enterocolitica and AvrA from Salmonella Typhimurium were also translocated via the Bartonella T4SS, while ByeA was not translocated via the Yersinia T3SS. Our data suggest that YopJ family T3SS effectors may have evolved from an ancestral T4SS effector, such as ByeA of Bartonella. In this evolutionary scenario, the signal for T4SS-dependent translocation encoded by N- and C-terminal sequences remained functional in the derived T3SS effectors due to the essential role these sequences coincidentally play in regulating acetyltransferase activity.
摘要：
进化保守的YopJ家族包含多种哺乳动物和植物病原体的许多III型分泌系统(T3SS)效应子,其乙酰化宿主蛋白以抑制免疫应答。乙酰化由中央乙酰转移酶结构域介导，该结构域侧翼为保守的调节序列，而非保守的N端扩展编码T3SS特异性易位信号。巴尔通菌属。是兼性细胞内病原体，在其哺乳动物储库中引起红细胞内菌血症，并在偶然感染的人类中引起多种疾病表现。Bartonellae不编码T3SS，但是大多数物种具有IV型分泌系统（T4SS），可以将巴尔通体效应蛋白（Beps）转移到宿主细胞中。在这里，我们报告了Bartonellae物种中存在的YopJ同源物代表了真正的T4SS效应物。像哺乳动物病原体的YopJ家族T3SS效应子，“BartonellaYopJ样效应物A”（ByeA）也靶向MAP激酶信号传导抑制促炎反应，然而,易位取决于功能T4SS。基于分裂NanoLuc荧光素酶的易位测定鉴定了在ByeA的C端和N端附近的保守调节区中T4SS依赖性易位所需的序列。小肠结肠炎耶尔森氏菌的T3SS效应子YopP和鼠伤寒沙门氏菌的AvrA也通过BartonellaT4SS易位，而ByeA没有通过耶尔森氏菌T3SS易位。我们的数据表明，YopJ家族T3SS效应子可能是从祖先的T4SS效应子进化而来的，例如Bartonella的ByeA。在这个进化场景中，由N和C末端序列编码的T4SS依赖性易位的信号在衍生的T3SS效应物中仍然具有功能，因为这些序列在调节乙酰转移酶活性中同时发挥了重要作用。
