Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Bioluminescent:Fluorescent Trypanosoma cruzi Reporter Strains as Tools for Exploring Chagas Disease Pathogenesis and Drug Activity

Author(s): Martin C. Taylor, Alexander I. Ward, Francisco Olmo, Amanda F. Francisco, Shiromani Jayawardhana, Fernanda C. Costa, Michael D. Lewis and John M. Kelly*

Volume 27, Issue 14, 2021

Published on: 24 November, 2020

Page: [1733 - 1740] Pages: 8

DOI: 10.2174/1381612826666201124113214

Price: $65

Abstract

Chagas disease results from infection with the trypanosomatid parasite Trypanosoma cruzi. Progress in developing new drugs has been hampered by the long term and complex nature of the condition and by our limited understanding of parasite biology. Technical difficulties in assessing the parasite burden during the chronic stage of infection have also proven to be a particular challenge. In this context, the development of noninvasive, highly sensitive bioluminescence imaging procedures based on parasites that express a red-shifted luciferase has greatly enhanced our ability to monitor infections in experimental models. Applications of this methodology have led to new insights into tissue tropism and infection dynamics and have been a major driver in drug development. The system has been further modified by the generation of parasite reporter lines that express bioluminescent:fluorescent fusion proteins, an advancement that has allowed chronic infections in mice to be examined at a cellular level. By exploiting bioluminescence, to identify the rare sites of tissue infection, and fluorescence to detect T. cruzi at the level of individual host cells in histological sections, it has been possible to investigate the replication and differentiation status of parasites in vivo and to examine the cellular environment of infection foci. In combination, these data provide a framework for the detailed dissection of disease pathogenesis and drug activity.

Keywords: Trypanosoma cruzi, in vivo imaging, bioluminescence, fluorescence, murine models, disease pathogenesis.

« Previous Next »
[1]
Molina I, Gómez i Prat J, Salvador F, et al. Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease. N Engl J Med 2014; 370(20): 1899-908.
[http://dx.doi.org/10.1056/NEJMoa1313122] [PMID: 24827034]
[2]
Morillo CA, Marin-Neto JA, Avezum A, et al. Randomized trial of benznidazole for chronic Chagas’ cardiomyopathy. N Engl J Med 2015; 373(14): 1295-306.
[http://dx.doi.org/10.1056/NEJMoa1507574] [PMID: 26323937]
[3]
Wilkinson SR, Taylor MC, Horn D, Kelly JM, Cheeseman I. A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes. Proc Natl Acad Sci USA 2008; 105(13): 5022-7.
[http://dx.doi.org/10.1073/pnas.0711014105] [PMID: 18367671]
[4]
Campos MCO, Leon LL, Taylor MC, Kelly JM. Benznidazole resistance in Trypanosoma cruzi: evidence that distinct mechanisms can act in concert . Mol Biochem Parasitol 2014; 193(1): 17-9..
[http://dx.doi.org/10.1016/j.molbiopara.2014.01.002] [PMID: 24462750]
[5]
Lang T, Goyard S, Lebastard M, Milon G. Bioluminescent Leishmania expressing luciferase for rapid and high throughput screening of drugs acting on amastigote-harbouring macrophages and for quantitative real-time monitoring of parasitism features in living mice . Cell Microbiol 2005; 7(3): 383-92..
[http://dx.doi.org/10.1111/j.1462-5822.2004.00468.x] [PMID: 15679841]
[6]
Hyland KV, Asfaw SH, Olson CL, Daniels MD, Engman DM. Bioluminescent imaging of Trypanosoma cruzi infection . Int J Parasitol 2008; 38(12): 1391-400..
[http://dx.doi.org/10.1016/j.ijpara.2008.04.002] [PMID: 18511053]
[7]
Myburgh E, Coles JA, Ritchie R, et al. In vivo imaging of trypanosome-brain interactions and development of a rapid screening test for drugs against CNS stage trypanosomiasis. PLoS Negl Trop Dis 2013; 7(8)e2384.
[http://dx.doi.org/10.1371/journal.pntd.0002384] [PMID: 23991236]
[8]
Claser C, Malleret B, Peng K, et al. Rodent Plasmodium-infected red blood cells: imaging their fates and interactions within their hosts. Parasitol Int 2014; 63(1): 187-94.
[http://dx.doi.org/10.1016/j.parint.2013.07.012] [PMID: 23892178]
[9]
Branchini BR, Ablamsky DM, Davis AL, et al. Red-emitting luciferases for bioluminescence reporter and imaging applications. Anal Biochem 2010; 396(2): 290-7.
[http://dx.doi.org/10.1016/j.ab.2009.09.009] [PMID: 19748472]
[10]
Lewis MD, Francisco AF, Taylor MC, Kelly JM. A new experimental model for assessing drug efficacy against Trypanosoma cruzi infection based on highly sensitive in vivo imaging. J Biomol Screen 2015; 20(1): 36-43. .
[http://dx.doi.org/10.1177/1087057114552623] [PMID: 25296657]
[11]
Lewis MD, Fortes Francisco A, Taylor MC, et al. Bioluminescence imaging of chronic Trypanosoma cruzi infections reveals tissue-specific parasite dynamics and heart disease in the absence of locally persistent infection. Cell Microbiol 2014; 16(9): 1285-300.
[http://dx.doi.org/10.1111/cmi.12297] [PMID: 24712539]
[12]
Lewis MD, Francisco AF, Taylor MC, Jayawardhana S, Kelly JM. Host and parasite genetics shape a link between Trypanosoma cruzi infection dynamics and chronic cardiomyopathy. Cell Microbiol 2016; 18(10): 1429-43.
[http://dx.doi.org/10.1111/cmi.12584] [PMID: 26918803]
[13]
Francisco AF, Lewis MD, Jayawardhana S, Taylor MC, Chatelain E, Kelly JM. The limited ability of posaconazole to cure both acute and chronic Trypanosoma cruzi infections revealed by highly sensitive in vivo imaging. Antimicrob Agents Chemother 2015; 59(8): 4653-61.
[http://dx.doi.org/10.1128/AAC.00520-15] [PMID: 26014936]
[14]
Francisco AF, Jayawardhana S, Lewis MD, et al. Nitroheterocyclic drugs cure experimental Trypanosoma cruzi infections more effectively in the chronic stage than in the acute stage. Sci Rep 2016; 6: 35351.
[http://dx.doi.org/10.1038/srep35351] [PMID: 27748443]
[15]
Brand S, Ko E-J, Viayna E, et al. Discovery and Optimization of 5-Amino-1,2,3-triazole-4-carboxamide Series against Trypanosoma cruzi. J Med Chem 2017; 60(17): 7284-99..
[http://dx.doi.org/10.1021/acs.jmedchem.7b00463] [PMID: 28844141]
[16]
Calvet CM, Choi JY, Thomas D, et al. 4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection. PLoS Negl Trop Dis 2017; 11(12), e0006132.
[http://dx.doi.org/10.1371/journal.pntd.0006132] [PMID: 29281643]
[17]
Mann GS, Francisco AF, Jayawardhana S, et al. Drug-cured experimental Trypanosoma cruzi infections confer long-lasting and cross-strain protection. PLoS Negl Trop Dis 2020; 14(4), e0007717.
[http://dx.doi.org/10.1371/journal.pntd.0007717] [PMID: 32302312]
[18]
Lewis MD, Francisco AF, Jayawardhana S, Langston H, Taylor MC, Kelly JM. Imaging the development of chronic Chagas disease after oral transmission. Sci Rep 2018; 8(1): 11292.
[http://dx.doi.org/10.1038/s41598-018-29564-7] [PMID: 30050153]
[19]
Lewis MD, Kelly JM. Putting Trypanosoma cruzi dynamics at the heart of Chagas disease. Trends Parasitol 2016; 32(11): 899-911.
[http://dx.doi.org/10.1016/j.pt.2016.08.009] [PMID: 27612651]
[20]
Francisco AF, Jayawardhana S, Taylor MC, Lewis MD, Kelly JM. Assessing the effectiveness of curative benznidazole treatment in preventing chronic cardiac pathology in experimental models of Chagas disease. Antimicrob Agents Chemother 2018; 62(10): e00832-18.
[http://dx.doi.org/10.1128/AAC.00832-18] [PMID: 30082291]
[21]
Sánchez-Valdéz FJ, Padilla A, Wang W, Orr D, Tarleton RL. Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure. eLife 2018; 7: 7.
[http://dx.doi.org/10.7554/eLife.34039] [PMID: 29578409]
[22]
Costa FC, Francisco AF, Jayawardhana S, et al. Expanding the toolbox for Trypanosoma cruzi: A parasite line incorporating a bioluminescence- fluorescence dual reporter and streamlined CRISPR/Cas9 functionality for rapid in vivo localisation and phenotyping. PLoS Negl Trop Dis 2018; 12(4): e0006388..
[http://dx.doi.org/10.1371/journal.pntd.0006388] [PMID: 29608569]
[23]
Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992; 119(3): 493-501.
[http://dx.doi.org/10.1083/jcb.119.3.493] [PMID: 1400587]
[24]
Salic A, Mitchison TJ. A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc Natl Acad Sci USA 2008; 105(7): 2415-20.
[http://dx.doi.org/10.1073/pnas.0712168105] [PMID: 18272492]
[25]
Taylor MC, Francisco AF, Jayawardhana S, et al. Exploiting genetically modified dual-reporter strains to monitor experimental Trypanosoma cruzi infections and host:parasite interactions Methods Mol Biol 2019; 1955: 147-63..
[http://dx.doi.org/10.1007/978-1-4939-9148-8_11] [PMID: 30868525]
[26]
Taylor MC, Ward A, Olmo F, et al. Intracellular DNA replication and differentiation of Trypanosoma cruzi is asynchronous within individual host cells in vivo at all stages of infection. PLoS Negl Trop Dis 2020; 14(3),: e0008007.
[http://dx.doi.org/10.1371/journal.pntd.0008007] [PMID: 32196491]
[27]
Sykes ML, Hilko DH, Kung LI, Poulsen SA, Avery VM. Investigation of pyrimidine nucleoside analogues as chemical probes to assess compound effects on the proliferation of Trypanosoma cruzi intracellular parasites. PLoS Negl Trop Dis 2020; 14(3), e0008068.
[http://dx.doi.org/10.1371/journal.pntd.0008068] [PMID: 32163414]
[28]
Mandyam CD, Harburg GC, Eisch AJ. Determination of key aspects of precursor cell proliferation, cell cycle length and kinetics in the adult mouse subgranular zone . Neuroscience 2007; 146(1): 108-22.
[http://dx.doi.org/10.1016/j.neuroscience.2006.12.064] [PMID: 17307295]
[29]
Almeida-de-Faria M, Freymüller E, Colli W, Alves MJ. Trypanosoma cruzi: characterization of an intracellular epimastigote-like form. Exp Parasitol 1999; 92(4): 263-74.
[http://dx.doi.org/10.1006/expr.1999.4423] [PMID: 10425154]
[30]
Tyler KM, Engman DM. The life cycle of Trypanosoma cruzi revisited . Int J Parasitol 2001; 31(5-6): 472-81..
[http://dx.doi.org/10.1016/S0020-7519(01)00153-9] [PMID: 11334932]
[31]
Kurup SP, Tarleton RL. The Trypanosoma cruzi flagellum is discarded via asymmetric cell division following invasion and provides early targets for protective CD8+ T cells. Cell Host Microbe 2014; 16(4): 439-49.
[http://dx.doi.org/10.1016/j.chom.2014.09.003] [PMID: 25299330]
[32]
Kessler RL, Contreras VT, Marliére NP, et al. Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host. Mol Microbiol 2017; 104(5): 712-36.
[http://dx.doi.org/10.1111/mmi.13653] [PMID: 28240790]
[33]
Francisco AF, Jayawardhana S, Lewis MD, Taylor MC, Kelly JM. Biological factors that impinge on Chagas disease drug development. Parasitology 2017; 144(14): 1871-80.
[http://dx.doi.org/10.1017/S0031182017001469] [PMID: 28831944]

Rights & Permissions Print Cite
Article Metrics
12
1
© 2024 Bentham Science Publishers | Privacy Policy