Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
Sainsbury Laboratory (SLCU), University of Cambridge, Cambridge CB2 1LR, UK.
Sci Adv. 2024 Oct 4;10(40):eado9516. doi: 10.1126/sciadv.ado9516.
Pathogens have evolved sophisticated mechanisms to manipulate host cell membrane dynamics, a crucial adaptation to survive in hostile environments shaped by innate immune responses. Plant-derived membrane interfaces, engulfing invasive hyphal projections of fungal and oomycete pathogens, are prominent junctures dictating infection outcomes. Understanding how pathogens transform these host-pathogen interfaces to their advantage remains a key biological question. Here, we identified a conserved effector, secreted by plant pathogenic oomycetes, that co-opts a host Rab GTPase-activating protein (RabGAP), TOPGAP, to remodel the host-pathogen interface. The effector, PiE354, hijacks TOPGAP as a susceptibility factor to usurp its GAP activity on Rab8a, a key Rab GTPase crucial for defense-related secretion. By hijacking TOPGAP, PiE354 purges Rab8a from the plasma membrane, diverting Rab8a-mediated immune trafficking away from the pathogen interface. This mechanism signifies an uncanny evolutionary adaptation of a pathogen effector in co-opting a host regulatory component to subvert defense-related secretion, thereby providing unprecedented mechanistic insights into the reprogramming of host membrane dynamics by pathogens.
病原体进化出了复杂的机制来操纵宿主细胞膜动力学，这是一种在先天免疫反应塑造的恶劣环境中生存的关键适应。植物衍生的膜接口，吞噬真菌和卵菌病原体入侵的菌丝突起，是决定感染结果的突出连接点。了解病原体如何将这些宿主-病原体界面转化为自身优势仍然是一个关键的生物学问题。在这里，我们鉴定了一种保守的效应物，由植物病原卵菌分泌，它可以利用宿主 Rab GTPase 激活蛋白 (RabGAP) TOPGAP 来重塑宿主-病原体界面。该效应物 PiE354 劫持 TOPGAP 作为易感性因子，篡夺其对 Rab8a 的 GAP 活性，Rab8a 是防御相关分泌所必需的关键 Rab GTPase。通过劫持 TOPGAP，PiE354 将 Rab8a 从质膜中清除，使 Rab8a 介导的免疫运输偏离病原体界面。这种机制标志着病原体效应物在利用宿主调节成分来颠覆防御相关分泌方面的惊人进化适应，从而为病原体对宿主膜动力学的重编程提供了前所未有的机制见解。
