Fridman Chaya Mushka, Keppel Kinga, Rudenko Vladislav, Altuna-Alvarez Jon, Albesa-Jové David, Bosis Eran, Salomon Dor
Department of Clinical Microbiology and Immunology, School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Instituto Biofisika (CSIC, UPV/EHU), Fundación Biofísica Bizkaia/Biofisika Bizkaia Fundazioa (FBB), Leioa, Spain.
PLoS Biol. 2025 Mar 17;23(3):e3003053. doi: 10.1371/journal.pbio.3003053. eCollection 2025 Mar.
Gram-negative bacteria employ the type VI secretion system (T6SS) to deliver toxic effectors into neighboring cells and outcompete rivals. Although many effectors have been identified, their secretion mechanism often remains unknown. Here, we describe WHIX, a domain sufficient to mediate the secretion of effectors via the T6SS. Remarkably, we find WHIX in T6SS effectors that contain a single toxic domain, as well as in effectors that contain two distinct toxic domains fused to either side of WHIX. We demonstrate that the latter, which we name double-blade effectors, require two cognate immunity proteins to antagonize their toxicity. Furthermore, we show that WHIX can be used as a chassis for T6SS-mediated secretion of multiple domains. Our findings reveal a new class of polymorphic T6SS cargo effectors with a unique secretion domain that can deploy two toxic domains in one shot, possibly reducing recipients' ability to defend themselves.
革兰氏阴性菌利用VI型分泌系统（T6SS）将毒性效应蛋白传递到邻近细胞中，并在竞争中胜过对手。尽管已经鉴定出了许多效应蛋白，但其分泌机制通常仍不清楚。在这里，我们描述了WHIX，这是一个足以介导效应蛋白通过T6SS进行分泌的结构域。值得注意的是，我们在含有单个毒性结构域的T6SS效应蛋白中发现了WHIX，以及在WHIX两侧融合有两个不同毒性结构域的效应蛋白中也发现了WHIX。我们证明，后者我们称为双刃效应蛋白，需要两种同源免疫蛋白来对抗其毒性。此外，我们表明WHIX可以用作T6SS介导的多个结构域分泌的底盘。我们的研究结果揭示了一类新的多态性T6SS货物效应蛋白，其具有独特的分泌结构域，可以一次性部署两个毒性结构域，可能会降低受体的自我防御能力。
