Numerical values for S3 Fig.

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.

革兰氏阴性菌可借助第六型分泌系统（type VI secretion system, T6SS）将毒性效应蛋白递送至邻近细胞，从而在菌群竞争中胜出。尽管已有诸多效应蛋白被鉴定，但其分泌机制大多仍未明确。本研究报道了WHIX结构域（domain），该结构域足以介导效应蛋白通过T6SS完成分泌。值得注意的是，研究团队在仅携带单个毒性结构域的T6SS效应蛋白中，以及在WHIX两侧融合有两种不同毒性结构域的效应蛋白中，均发现了该结构域。本研究证实，这类被我们命名为双刃效应蛋白的分子，需要两种同源免疫蛋白才能拮抗其毒性作用。此外，研究表明WHIX可作为骨架载体，用于通过T6SS介导多种结构域的分泌。本研究的发现揭示了一类全新的多态性T6SS负载效应蛋白，其拥有独特的分泌结构域，可单次递送两个毒性结构域，或可降低受体细胞的防御能力。