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

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.

MeSH terms

  • Animals
  • Chagas Disease* / parasitology
  • Disease Models, Animal
  • Female
  • Genes, Reporter
  • Genetic Variation
  • Genotype
  • Host-Parasite Interactions
  • Humans
  • Luminescent Measurements / methods
  • Mice
  • Phenotype
  • Trypanosoma cruzi* / drug effects
  • Trypanosoma cruzi* / genetics

Grants and funding

This work was supported by UK Medical Research Council (MRC) grants MR/T015969/1 to J.M.K. and MR/R021430/1 to M.D.L. AIW was in receipt of an MRC LID (DTP) Studentship (MR/N013638/1). Drugs for Neglected Diseases initiative (DNDi) was awarded to JMK. DNDi received financial support from: Department for International Development (DFID), UK; Federal Ministry of Education and Research (BMBF) through KfW, Germany; and Médecins sans Frontières (MSF) International. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.