The remarkable variety of microbial species of human pathogens and microbiomes generates significant quantities of secreted amyloids, which are structured protein fibrils that serve diverse functions related to virulence and interactions with the host. Human amyloids are associated largely with fatal neurodegenerative and systemic aggregation diseases, and current research has put forward the hypothesis that the interspecies amyloid interactome has physiological and pathological significance. Moreover, functional and molecular-level connections between antimicrobial activity and amyloid structures suggest a neuroimmune role for amyloids that are otherwise known to be pathological. Compared to the extensive structural information that has been accumulated for human amyloids, high-resolution structures of microbial and antimicrobial amyloids are only emerging. These recent structures reveal both similarities and surprising departures from the typical amyloid motif, in accordance with their diverse activities, and advance the discovery of novel antivirulence and antimicrobial agents. In addition, the structural information has led researchers to postulate that amyloidogenic sequences are natural targets for structural mimicry, for instance in host–microbe interactions. Microbial amyloid research could ultimately be used to fight aggressive infections and possibly processes leading to autoimmune and neurodegenerative diseases.

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微生物和抗菌淀粉样蛋白的结构拟态

人类病原体和微生物组的微生物物种种类繁多，会产生大量的分泌型淀粉样蛋白，这些淀粉样蛋白是结构蛋白原纤维，具有与毒力和与宿主相互作用相关的多种功能。人类淀粉样蛋白在很大程度上与致命的神经退行性和系统性聚集疾病相关，目前的研究提出了种间淀粉样蛋白相互作用组具有生理和病理意义的假设。此外，抗菌活性和淀粉样蛋白结构之间的功能和分子水平联系表明淀粉样蛋白具有神经免疫作用，而淀粉样蛋白在其他方面已知是病理性的。与人类淀粉样蛋白已积累的广泛结构信息相比，微生物和抗菌淀粉样蛋白的高分辨率结构才刚刚出现。这些最新结构根据其不同的活性揭示了与典型淀粉样蛋白基序的相似性和令人惊讶的差异，并推进了新型抗毒剂和抗菌剂的发现。此外，结构信息使研究人员推测淀粉样蛋白生成序列是结构拟态的天然目标，例如在宿主与微生物的相互作用中。微生物淀粉样蛋白研究最终可用于对抗侵袭性感染以及可能导致自身免疫和神经退行性疾病的过程。