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

一组表型和基因型多样的生物发光:荧光克氏锥虫菌株可作为恰加斯病研究的资源

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作者:Francisco Olmo, Shiromani Jayawardhana, Archie A Khan, Harry C Langston, Amanda Fortes Francisco, Richard L Atherton, Alex I Ward, Martin C Taylor, John M Kelly, Michael D Lewis

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.

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