Höfling Sabrina, Grabowski Benjamin, Norkowski Stefanie, Schmidt M Alexander, Rüter Christian
Institute of Infectiology - Center for Molecular Biology of Inflammation (ZMBE), University of Münster, Germany.
Institute of Infectiology - Center for Molecular Biology of Inflammation (ZMBE), University of Münster, Germany.
Int J Med Microbiol. 2015 May;305(3):424-32. doi: 10.1016/j.ijmm.2015.03.009. Epub 2015 Apr 1.
Yersinia outer protein M (YopM) belongs to the group of Yop effector proteins, which are highly conserved among pathogenic Yersinia species. During infection, the effectors are delivered into the host cell cytoplasm via the type 3 secretion system to subvert the host immune response and support the survival of Yersinia. In contrast to the other Yop effectors, YopM does not possess a known enzymatic activity and its molecular mechanism(s) of action remain(s) poorly understood. However, YopM was shown to promote colonization and dissemination of Yersinia, thus being crucial for the pathogen's virulence in vivo. Moreover, YopM interacts with several host cell proteins and might utilize them to execute its anti-inflammatory activities. The results obtained so far indicate that YopM is a multifunctional protein that counteracts the host immune defense by multiple activities, which are at least partially independent of each other. Finally, its functions seem to be also influenced by differences between the specific YopM isoforms expressed by Yersinia subspecies. In this review, we focus on the global as well as more specific contribution of YopM to virulence of Yersinia during infection and point out the various extra- and intracellular molecular functions of YopM. In addition, the novel cell-penetrating ability of recombinant YopM and its potential applications as a self-delivering immunomodulatory therapeutic will be discussed.
耶尔森氏菌外蛋白M（YopM）属于Yop效应蛋白组，这类蛋白在致病性耶尔森氏菌物种中高度保守。在感染过程中，效应蛋白通过III型分泌系统被递送到宿主细胞质中，以破坏宿主免疫反应并支持耶尔森氏菌的存活。与其他Yop效应蛋白不同，YopM不具有已知的酶活性，其作用的分子机制仍知之甚少。然而，YopM已被证明可促进耶尔森氏菌的定殖和传播，因此对该病原体在体内的毒力至关重要。此外，YopM与几种宿主细胞蛋白相互作用，并可能利用它们来发挥其抗炎活性。迄今为止获得的结果表明，YopM是一种多功能蛋白，通过多种活动对抗宿主免疫防御，这些活动至少部分相互独立。最后，其功能似乎也受到耶尔森氏菌亚种表达的特定YopM亚型之间差异的影响。在这篇综述中，我们重点关注YopM在感染期间对耶尔森氏菌毒力的整体以及更具体的贡献，并指出YopM的各种细胞外和细胞内分子功能。此外，还将讨论重组YopM新的细胞穿透能力及其作为自递送免疫调节疗法的潜在应用。
