Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Modeling and Informatics, Denali Therapeutics, South San Francisco, CA 94080, USA.
Cell. 2020 Dec 10;183(6):1562-1571.e12. doi: 10.1016/j.cell.2020.10.042.
Ticks transmit a diverse array of microbes to vertebrate hosts, including human pathogens, which has led to a human-centric focus in this vector system. Far less is known about pathogens of ticks themselves. Here, we discover that a toxin in blacklegged ticks (Ixodes scapularis) horizontally acquired from bacteria-called domesticated amidase effector 2 (dae2)-has evolved to kill mammalian skin microbes with remarkable efficiency. Secreted into the saliva and gut of ticks, Dae2 limits skin-associated staphylococci in ticks while feeding. In contrast, Dae2 has no intrinsic ability to kill Borrelia burgdorferi, the tick-borne Lyme disease bacterial pathogen. These findings suggest ticks resist their own pathogens while tolerating symbionts. Thus, just as tick symbionts can be pathogenic to humans, mammalian commensals can be harmful to ticks. Our study underscores how virulence is context-dependent and bolsters the idea that "pathogen" is a status and not an identity.
蜱虫将多种微生物传播给脊椎动物宿主，包括人类病原体，这导致人们对这种载体系统的关注集中在人类身上。然而，蜱虫自身病原体的相关知识却知之甚少。在这里，我们发现，黑腿蜱（Ixodes scapularis）从细菌中水平获得的一种毒素——被驯化的酰胺酶效应物 2（dae2）——已经进化到能够以惊人的效率杀死哺乳动物皮肤微生物。dae2 分泌到蜱虫的唾液和肠道中，在蜱虫进食时限制了与皮肤相关的葡萄球菌。相比之下，dae2 本身没有杀死伯氏疏螺旋体（Borrelia burgdorferi）的能力，伯氏疏螺旋体是 tick-borne Lyme 病的细菌病原体。这些发现表明，蜱虫在抵抗自身病原体的同时，也容忍共生体。因此，正如 tick 共生体可能对人类具有致病性一样，哺乳动物共生体也可能对蜱虫造成危害。我们的研究强调了毒力是如何依赖于环境的，并支持了“病原体”是一种状态而不是一种身份的观点。
