Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.
Department of Chemistry, Duke University, Durham, NC, USA.
Curr Opin Chem Biol. 2023 Aug;75:102316. doi: 10.1016/j.cbpa.2023.102316. Epub 2023 May 14.
Intracellular protozoan parasites are responsible for wide-spread infectious diseases. These unicellular pathogens have complex, multi-host life cycles, which present challenges for investigating their basic biology and for discovering vulnerabilities that could be exploited for disease control. Throughout development, parasite proteomes are dynamic and support stage-specific functions, but detection of these proteins is often technically challenging and complicated by the abundance of host proteins. Thus, to elucidate key parasite processes and host-pathogen interactions, labeling strategies are required to track pathogen proteins during infection. Herein, we discuss the application of bioorthogonal non-canonical amino acid tagging and proximity-dependent labeling to broadly study protozoan parasites and include outlooks for future applications to study Plasmodium, the causative agent of malaria. We highlight the potential of these technologies to provide spatiotemporal labeling with selective parasite protein enrichment, which could enable previously unattainable insight into the biology of elusive developmental stages.
细胞内原生动物寄生虫是广泛传播传染病的罪魁祸首。这些单细胞病原体具有复杂的多宿主生命周期,这给研究其基础生物学和发现可用于疾病控制的弱点带来了挑战。在整个发育过程中,寄生虫蛋白质组是动态的,支持特定阶段的功能,但这些蛋白质的检测通常在技术上具有挑战性,并因宿主蛋白质的丰富而变得复杂。因此,为了阐明关键的寄生虫过程和宿主-病原体相互作用,需要标记策略来跟踪感染过程中的病原体蛋白。本文讨论了生物正交非天然氨基酸标记和邻近依赖性标记在广泛研究原生动物寄生虫中的应用,并展望了未来在疟疾病原体疟原虫研究中的应用。我们强调了这些技术提供时空标记和选择性寄生虫蛋白富集的潜力,这可能使以前难以捉摸的发育阶段的生物学研究成为可能。