Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.

<h4>Background</h4>Iron is an essential element for the survival of microorganisms in vitro and in vivo, acting as a cofactor of several enzymes and playing a critical role in host-parasite relationships. Leishmania (Viannia) braziliensis is a parasite that is widespread in the new world...

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Autores principales:	Camila Mesquita-Rodrigues, Rubem F S Menna-Barreto, Leonardo Sabóia-Vahia, Silvia A G Da-Silva, Elen M de Souza, Mariana C Waghabi, Patrícia Cuervo, José B De Jesus
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/4f8b482a467246179885ef96018684dd
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spelling	oai:doaj.org-article:4f8b482a467246179885ef96018684dd2021-11-18T09:16:47ZCellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.1935-27271935-273510.1371/journal.pntd.0002481https://doaj.org/article/4f8b482a467246179885ef96018684dd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24147167/pdf/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Iron is an essential element for the survival of microorganisms in vitro and in vivo, acting as a cofactor of several enzymes and playing a critical role in host-parasite relationships. Leishmania (Viannia) braziliensis is a parasite that is widespread in the new world and considered the major etiological agent of American tegumentary leishmaniasis. Although iron depletion leads to promastigote and amastigote growth inhibition, little is known about the role of iron in the biology of Leishmania. Furthermore, there are no reports regarding the importance of iron for L. (V.) braziliensis.<h4>Methodology/principal findings</h4>In this study, the effect of iron on the growth, ultrastructure and protein expression of L. (V.) braziliensis was analyzed by the use of the chelator 2,2-dipyridyl. Treatment with 2,2-dipyridyl affected parasites' growth in a dose- and time-dependent manner. Multiplication of the parasites was recovered after reinoculation in fresh culture medium. Ultrastructural analysis of treated promastigotes revealed marked mitochondrial swelling with loss of cristae and matrix and the presence of concentric membranar structures inside the organelle. Iron depletion also induced Golgi disruption and intense cytoplasmic vacuolization. Fluorescence-activated cell sorting analysis of tetramethylrhodamine ester-stained parasites showed that 2,2-dipyridyl collapsed the mitochondrial membrane potential. The incubation of parasites with propidium iodide demonstrated that disruption of mitochondrial membrane potential was not associated with plasma membrane permeabilization. TUNEL assays indicated no DNA fragmentation in chelator-treated promastigotes. In addition, two-dimensional electrophoresis showed that treatment with the iron chelator induced up- or down-regulation of proteins involved in metabolism of nucleic acids and coordination of post-translational modifications, without altering their mRNA levels.<h4>Conclusions</h4>Iron chelation leads to a multifactorial response that results in cellular collapse, starting with the interruption of cell proliferation and culminating in marked mitochondrial impairment in some parasites and their subsequent cell death, whereas others may survive and resume proliferating.Camila Mesquita-RodriguesRubem F S Menna-BarretoLeonardo Sabóia-VahiaSilvia A G Da-SilvaElen M de SouzaMariana C WaghabiPatrícia CuervoJosé B De JesusPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 7, Iss 10, p e2481 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Camila Mesquita-Rodrigues Rubem F S Menna-Barreto Leonardo Sabóia-Vahia Silvia A G Da-Silva Elen M de Souza Mariana C Waghabi Patrícia Cuervo José B De Jesus Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.
description	<h4>Background</h4>Iron is an essential element for the survival of microorganisms in vitro and in vivo, acting as a cofactor of several enzymes and playing a critical role in host-parasite relationships. Leishmania (Viannia) braziliensis is a parasite that is widespread in the new world and considered the major etiological agent of American tegumentary leishmaniasis. Although iron depletion leads to promastigote and amastigote growth inhibition, little is known about the role of iron in the biology of Leishmania. Furthermore, there are no reports regarding the importance of iron for L. (V.) braziliensis.<h4>Methodology/principal findings</h4>In this study, the effect of iron on the growth, ultrastructure and protein expression of L. (V.) braziliensis was analyzed by the use of the chelator 2,2-dipyridyl. Treatment with 2,2-dipyridyl affected parasites' growth in a dose- and time-dependent manner. Multiplication of the parasites was recovered after reinoculation in fresh culture medium. Ultrastructural analysis of treated promastigotes revealed marked mitochondrial swelling with loss of cristae and matrix and the presence of concentric membranar structures inside the organelle. Iron depletion also induced Golgi disruption and intense cytoplasmic vacuolization. Fluorescence-activated cell sorting analysis of tetramethylrhodamine ester-stained parasites showed that 2,2-dipyridyl collapsed the mitochondrial membrane potential. The incubation of parasites with propidium iodide demonstrated that disruption of mitochondrial membrane potential was not associated with plasma membrane permeabilization. TUNEL assays indicated no DNA fragmentation in chelator-treated promastigotes. In addition, two-dimensional electrophoresis showed that treatment with the iron chelator induced up- or down-regulation of proteins involved in metabolism of nucleic acids and coordination of post-translational modifications, without altering their mRNA levels.<h4>Conclusions</h4>Iron chelation leads to a multifactorial response that results in cellular collapse, starting with the interruption of cell proliferation and culminating in marked mitochondrial impairment in some parasites and their subsequent cell death, whereas others may survive and resume proliferating.
format	article
author	Camila Mesquita-Rodrigues Rubem F S Menna-Barreto Leonardo Sabóia-Vahia Silvia A G Da-Silva Elen M de Souza Mariana C Waghabi Patrícia Cuervo José B De Jesus
author_facet	Camila Mesquita-Rodrigues Rubem F S Menna-Barreto Leonardo Sabóia-Vahia Silvia A G Da-Silva Elen M de Souza Mariana C Waghabi Patrícia Cuervo José B De Jesus
author_sort	Camila Mesquita-Rodrigues
title	Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.
title_short	Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.
title_full	Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.
title_fullStr	Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.
title_full_unstemmed	Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.
title_sort	cellular growth and mitochondrial ultrastructure of leishmania (viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4f8b482a467246179885ef96018684dd
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Cellular growth and mitochondrial ultrastructure of leishmania (Viannia) braziliensis promastigotes are affected by the iron chelator 2,2-dipyridyl.

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