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Acriflavine treatment promotes dyskinetoplasty in Trypanosoma cruzi as revealed by ultrastructural analysis

Published online by Cambridge University Press:  21 August 2013

THIAGO MANCHESTER ,
DANIELLE PEREIRA CAVALCANTI ,
MARCELO ZOGOVICH ,
WANDERLEY DE SOUZA  and
MARIA CRISTINA MACHADO MOTTA
THIAGO MANCHESTER
Affiliation:
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, RJ, Brazil
DANIELLE PEREIRA CAVALCANTI
Affiliation:
Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, RJ, Brazil Diretoria de Metrologia Aplicada às Ciências da Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia-Inmetro, RJ, Brazil
MARCELO ZOGOVICH
Affiliation:
Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, RJ, Brazil Diretoria de Metrologia Aplicada às Ciências da Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia-Inmetro, RJ, Brazil
WANDERLEY DE SOUZA
Affiliation:
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, RJ, Brazil Diretoria de Metrologia Aplicada às Ciências da Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia-Inmetro, RJ, Brazil
MARIA CRISTINA MACHADO MOTTA*
Affiliation:
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, RJ, Brazil
*
*Corresponding author: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Centro de Ciências da Saúde, Bloco G, subsolo, Rio de Janeiro, RJ, CEP 21949-900, Brazil. E-mail: [email protected]
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Summary

Trypanosomatid mitochondrial DNA is structured as a giant network of thousands of interlocked DNA molecules enclosed within the kinetoplast. The structure and replication mechanism of kinetoplast DNA (kDNA) is unique, thereby making it an excellent chemotherapeutic target. Alteration in the structural organization of kDNA can give rise to dyskinetoplastic (Dk) strains. In Dk cells, the kDNA is dispersed in clumps throughout the mitochondrial matrix and not organized into a network. In this work, Trypanosoma cruzi epimastigotes were treated with acriflavine, a DNA intercalating drug, which promoted a decrease in cell proliferation and induced the appearance of Dk protozoa. In treated cells, the kinetoplast lost its normal disc-shaped structure because the fibrillar arrangement was reduced to a compact, amorphous mass within the mitochondrion. Moreover, basic proteins associated with kDNA were redistributed throughout the Dk protozoal kinetoplast. We sought to understand how the disruption of the kDNA leads to the emergence of the Dk phenotype with atomic force microscopy (AFM) analysis of isolated networks. Our results demonstrate that the detachment of minicircles from the kDNA disk promotes the disassembly of the network, thereby generating Dk cells. Our data strongly suggest that acriflavine inhibits T. cruzi multiplication by interfering with kDNA replication.

Keywords

AcriflavinedyskinetoplastykinetoplastTrypanosoma cruziatomic force microscopyultrastructure
Type
Research Article
Information
Parasitology , Volume 140 , Issue 11 , September 2013 , pp. 1422 - 1431
Copyright
Copyright © Cambridge University Press 2013 

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