美国弗雷德·哈钦森癌症中心Aaron M. Ring等研究人员合作发现，人类病媒微生物相互作用图谱揭示致病机制。2024年6月13日，《细胞》杂志在线发表了这项成果。
研究人员利用细菌选择来阐明宿主与微生物之间的高通量相互作用（BASEHIT），这是一种能够检测微生物与3324种人类外蛋白相互作用的技术，对82种人类病原体样本的相互作用组进行了分析，其中包括30株节肢动物传播的病原体和8株相关的非媒介传播病原体。由此产生的图谱揭示了1303种推测的相互作用，其中包括数百种在致病过程中可能发挥作用的配对，包括细胞入侵、组织定植、免疫逃避和宿主感应。
随后的功能研究发现，莱姆病螺旋体能识别表皮生长因子作为转录调控的环境线索，细胞内病原体与硫氧还蛋白之间的保守相互作用促进了细胞入侵。总之，该相互作用组图谱提供了分子水平的微生物致病机理见解，并揭示了下一代疗法的潜在宿主导向靶标。
据介绍，病媒传播疾病是全球死亡的主要原因之一，也是一项尚未得到满足的巨大医疗需求。病原体与宿主细胞外蛋白质（“外蛋白质组”）的结合是病媒传播疾病病因学中的一个关键界面。
附：英文原文
Title: An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms
Author: Thomas M. Hart, Nicole D. Sonnert, Xiaotian Tang, Reetika Chaurasia, Paige E. Allen, Jason R. Hunt, Curtis B. Read, Emily E. Johnson, Gunjan Arora, Yile Dai, Yingjun Cui, Yu-Min Chuang, Qian Yu, M. Sayeedur Rahman, M. Tays Mendes, Agustin Rolandelli, Pallavi Singh, Abhai K. Tripathi, Choukri Ben Mamoun, Melissa J. Caimano, Justin D. Radolf, Yi-Pin Lin, Volker Fingerle, Gabriele Margos, Utpal Pal, Raymond M. Johnson, Joao H.F. Pedra, Abdu F. Azad, Jeanne Salje, George Dimopoulos, Joseph M. Vinetz, Jason A. Carlyon, Noah W. Palm, Erol Fikrig, Aaron M. Ring
Issue&Volume: 2024-06-13
Abstract: Vector-borne diseases are a leading cause of death worldwide and pose a substantialunmet medical need. Pathogens binding to host extracellular proteins (the “exoproteome”)represents a crucial interface in the etiology of vector-borne disease. Here, we usedbacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)—atechnique enabling interrogation of microbial interactions with 3,324 human exoproteins—toprofile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-bornepathogens and 8 strains of related non-vector-borne pathogens. The resulting atlasrevealed 1,303 putative interactions, including hundreds of pairings with potentialroles in pathogenesis, including cell invasion, tissue colonization, immune evasion,and host sensing. Subsequent functional investigations uncovered that Lyme diseasespirochetes recognize epidermal growth factor as an environmental cue of transcriptionalregulation and that conserved interactions between intracellular pathogens and thioredoxinsfacilitate cell invasion. In summary, this interactome atlas provides molecular-levelinsights into microbial pathogenesis and reveals potential host-directed targets fornext-generation therapeutics.
DOI: 10.1016/j.cell.2024.05.023
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00532-4