Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
Department of Microbiology, Immunology and Molecular Genetics, Geffen School of Medicine at UCLA, University of California, Los Angeles, California, United States of America.
PLoS Negl Trop Dis. 2019 Jul 25;13(7):e0007424. doi: 10.1371/journal.pntd.0007424. eCollection 2019 Jul.
In this review, we summarize the current knowledge concerning the eukaryotic protozoan parasite Leishmania tarentolae, with a main focus on its potential for biotechnological applications. We will also discuss the genus, subgenus, and species-level classification of this parasite, its life cycle and geographical distribution, and similarities and differences to human-pathogenic species, as these aspects are relevant for the evaluation of biosafety aspects of L. tarentolae as host for recombinant DNA/protein applications. Studies indicate that strain LEM-125 but not strain TARII/UC of L. tarentolae might also be capable of infecting mammals, at least transiently. This could raise the question of whether the current biosafety level of this strain should be reevaluated. In addition, we will summarize the current state of biotechnological research involving L. tarentolae and explain why this eukaryotic parasite is an advantageous and promising human recombinant protein expression host. This summary includes overall biotechnological applications, insights into its protein expression machinery (especially on glycoprotein and antibody fragment expression), available expression vectors, cell culture conditions, and its potential as an immunotherapy agent for human leishmaniasis treatment. Furthermore, we will highlight useful online tools and, finally, discuss possible future applications such as the humanization of the glycosylation profile of L. tarentolae or the expression of mammalian recombinant proteins in amastigote-like cells of this species or in amastigotes of avirulent human-pathogenic Leishmania species.
在这篇综述中,我们总结了真核原生动物寄生虫利什曼原虫的现有知识,主要关注其在生物技术应用方面的潜力。我们还将讨论这种寄生虫的属、亚属和种分类、生命周期和地理分布,以及与人类致病性物种的相似性和差异性,因为这些方面对于评估利什曼原虫作为重组 DNA/蛋白质应用宿主的生物安全性方面是相关的。研究表明,利什曼原虫的 LEM-125 株而不是 TARII/UC 株可能也有能力感染哺乳动物,至少是短暂的。这可能会引发一个问题,即是否应该重新评估这种菌株的当前生物安全性水平。此外,我们将总结涉及利什曼原虫的生物技术研究的现状,并解释为什么这种真核寄生虫是一种有利和有前途的人类重组蛋白表达宿主。这一总结包括生物技术的整体应用、对其蛋白质表达机制(特别是糖蛋白和抗体片段表达)的深入了解、可用的表达载体、细胞培养条件,以及作为人类利什曼病治疗的免疫疗法药物的潜力。此外,我们将重点介绍有用的在线工具,最后讨论可能的未来应用,如利什曼原虫糖基化谱的人源化,或在该物种的类似无鞭毛体细胞或无毒性人类致病性利什曼物种的无鞭毛体中表达哺乳动物重组蛋白。