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一组表型和基因型多样化的生物发光:荧光克氏锥虫菌株作为恰加斯病研究的资源。

A panel of phenotypically and genotypically diverse bioluminescent:fluorescent Trypanosoma cruzi strains as a resource for Chagas disease research.

机构信息

Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

出版信息

PLoS Negl Trop Dis. 2024 May 31;18(5):e0012106. doi: 10.1371/journal.pntd.0012106. eCollection 2024 May.

Abstract

Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite that displays considerable genetic diversity. Infections result in a range of pathological outcomes, and different strains can exhibit a wide spectrum of anti-parasitic drug tolerance. The genetic determinants of infectivity, virulence and therapeutic susceptibility remain largely unknown. As experimental tools to address these issues, we have generated a panel of bioluminescent:fluorescent parasite strains that cover the diversity of the T. cruzi species. These reporters allow spatio-temporal infection dynamics in murine models to be monitored in a non-invasive manner by in vivo imaging, provide a capability to detect rare infection foci at single-cell resolution, and represent a valuable resource for investigating virulence and host:parasite interactions at a mechanistic level. Importantly, these parasite reporter strains can also contribute to the Chagas disease drug screening cascade by ensuring that candidate compounds have pan-species in vivo activity prior to being advanced into clinical testing. The parasite strains described in this paper are available on request.

摘要

克氏锥虫病由原生动物寄生虫克氏锥虫引起,该寄生虫具有相当大的遗传多样性。感染会导致一系列病理结果,并且不同的菌株可能表现出广泛的抗寄生虫药物耐药性。感染性、毒力和治疗敏感性的遗传决定因素在很大程度上仍然未知。作为解决这些问题的实验工具,我们生成了一组生物发光:荧光寄生虫株,涵盖了克氏锥虫物种的多样性。这些报告器允许通过体内成像以非侵入性的方式监测小鼠模型中的时空感染动态,提供以单细胞分辨率检测罕见感染焦点的能力,并代表一种有价值的资源,可用于在机制水平上研究毒力和宿主:寄生虫相互作用。重要的是,这些寄生虫报告株还可以通过确保候选化合物在进入临床测试之前具有全物种的体内活性,从而为克氏锥虫病药物筛选级联做出贡献。本文中描述的寄生虫株可应要求提供。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1099/11168640/4e80338c9267/pntd.0012106.g001.jpg

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