The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghScotland, United Kingdom.
Front Cell Infect Microbiol. 2017 Jul 19;7:333. doi: 10.3389/fcimb.2017.00333. eCollection 2017.
is an intracellular bacterial pathogen and the causative agent of melioidosis, a severe disease of humans and animals. Like other clinically important Gram-negative bacteria, fundamental to pathogenesis is the Bsa Type III Secretion System. The Bsa system injects bacterial effector proteins into the cytoplasm of target host cells subverting cellular pathways for the benefit of the bacteria. It is required for invasion of non-phagocytic host cells, escape from the endocytic compartment into the host cell cytoplasm, and for virulence in murine models of melioidosis. We have recently described the repertoire of effector proteins secreted by the Bsa system, however the functions of many of these effector proteins remain an enigma. One such protein is BipC, a homolog of the translocator/effector proteins SipC and IpaC from spp. and respectively. SipC and IpaC each have separate and distinct roles acting both as translocators, involved in creating a pore in the eukaryotic cell membrane through which effector proteins can transit, and as effectors by interacting with and polymerizing host cell actin. In this study, pull-down assays demonstrate an interaction between BipC and actin. Furthermore, we show that BipC directly interacts with actin, preferentially with actin polymers (F-actin) and has the ability to polymerize actin in a similar manner as that described for SipC. Yet unlike SipC, BipC does not stabilize F-actin filaments, indicating a functionally distinct interaction with actin. Expression of Myc-tagged BipC in HeLa cells induces the formation of pseudopodia similar to that seen for IpaC. This study explores the effector function of BipC and reveals that actin interaction is conserved within the BipC/SipC/IpaC family of translocator/effector proteins.
是一种细胞内细菌病原体，也是类鼻疽病的病原体，这是一种人类和动物的严重疾病。与其他临床重要的革兰氏阴性菌一样，发病机制的基础是 Bsa 型 III 型分泌系统。该系统将细菌效应蛋白注入靶宿主细胞的细胞质中，使宿主细胞的途径发生改变，从而有利于细菌。它是侵入非吞噬宿主细胞、从吞噬体小泡逃逸到宿主细胞质以及在类鼻疽病的小鼠模型中产生毒力所必需的。我们最近描述了 Bsa 系统分泌的效应蛋白库，然而，这些效应蛋白的许多功能仍然是个谜。其中一种蛋白是 BipC，它是 spp. 和 中的转运蛋白/效应蛋白 SipC 和 IpaC 的同源物。SipC 和 IpaC 各有不同的作用，既是转运体，通过在真核细胞膜上形成一个孔，使效应蛋白能够通过，又是效应蛋白，与肌动蛋白相互作用并聚合宿主细胞肌动蛋白。在这项研究中，下拉实验证明了 BipC 与肌动蛋白之间的相互作用。此外，我们还表明，BipC 直接与肌动蛋白相互作用，优先与肌动蛋白聚合物（F-肌动蛋白）相互作用，并具有类似于 SipC 描述的聚合肌动蛋白的能力。然而，与 SipC 不同的是，BipC 不会稳定 F-肌动蛋白丝，表明与肌动蛋白的相互作用具有不同的功能。在 HeLa 细胞中表达 Myc 标记的 BipC 会诱导类似于 IpaC 所见的伪足形成。这项研究探索了 BipC 的效应子功能，并揭示了肌动蛋白相互作用在 BipC/SipC/IpaC 家族的转运蛋白/效应蛋白中是保守的。
