Translocation of YopJ family effector proteins through the VirB/VirD4 T4SS of Bartonella

• 成果类型: Article
• 署名作者: Fromm, Katja; Ortelli, Monica; Boegli, Alexandra; Dehio, Christoph
• 署名单位: University of Basel; University of Lausanne
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13701
• DOI: 10.1073/pnas.2310348121
• 发表日期: 2024-05-14
• 关键词: necrosis-factor-alpha; iv secretion system; iii secretion; yersinia-enterocolitica; kinase activation; macrophages; signal; plant; identification; transcription

摘要

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.