Leishmania metacyclogenesis is promoted in the absence of purines.

Leishmania parasites, the causative agent of leishmaniasis, are transmitted through the bite of an infected sand fly. Leishmania parasites present two basic forms known as promastigote and amastigote which, respectively, parasitizes the vector and the mammalian hosts. Infection of the vertebrate hos...

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Autores principales: Tiago Donatelli Serafim, Amanda Braga Figueiredo, Pedro Augusto Carvalho Costa, Eduardo Almeida Marques-da-Silva, Ricardo Gonçalves, Sandra Aparecida Lima de Moura, Nelder Figueiredo Gontijo, Sydnei Magno da Silva, Marilene Suzan Marques Michalick, José Roberto Meyer-Fernandes, Roberto Paes de Carvalho, Silvia Reni Bortolin Uliana, Juliana Lopes Rangel Fietto, Luís Carlos Crocco Afonso
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:5806430d98d24e3e98e9ff43318daddb2021-11-18T09:15:48ZLeishmania metacyclogenesis is promoted in the absence of purines.1935-27271935-273510.1371/journal.pntd.0001833https://doaj.org/article/5806430d98d24e3e98e9ff43318daddb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23050028/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735Leishmania parasites, the causative agent of leishmaniasis, are transmitted through the bite of an infected sand fly. Leishmania parasites present two basic forms known as promastigote and amastigote which, respectively, parasitizes the vector and the mammalian hosts. Infection of the vertebrate host is dependent on the development, in the vector, of metacyclic promastigotes, however, little is known about the factors that trigger metacyclogenesis in Leishmania parasites. It has been generally stated that "stressful conditions" will lead to development of metacyclic forms, and with the exception of a few studies no detailed analysis of the molecular nature of the stress factor has been performed. Here we show that presence/absence of nucleosides, especially adenosine, controls metacyclogenesis both in vitro and in vivo. We found that addition of an adenosine-receptor antagonist to in vitro cultures of Leishmania amazonensis significantly increases metacyclogenesis, an effect that can be reversed by the presence of specific purine nucleosides or nucleobases. Furthermore, our results show that proliferation and metacyclogenesis are independently regulated and that addition of adenosine to culture medium is sufficient to recover proliferative characteristics for purified metacyclic promastigotes. More importantly, we show that metacyclogenesis was inhibited in sand flies infected with Leishmania infantum chagasi that were fed a mixture of sucrose and adenosine. Our results fill a gap in the life cycle of Leishmania parasites by demonstrating how metacyclogenesis, a key point in the propagation of the parasite to the mammalian host, can be controlled by the presence of specific purines.Tiago Donatelli SerafimAmanda Braga FigueiredoPedro Augusto Carvalho CostaEduardo Almeida Marques-da-SilvaRicardo GonçalvesSandra Aparecida Lima de MouraNelder Figueiredo GontijoSydnei Magno da SilvaMarilene Suzan Marques MichalickJosé Roberto Meyer-FernandesRoberto Paes de CarvalhoSilvia Reni Bortolin UlianaJuliana Lopes Rangel FiettoLuís Carlos Crocco AfonsoPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 6, Iss 9, p e1833 (2012)
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
Tiago Donatelli Serafim
Amanda Braga Figueiredo
Pedro Augusto Carvalho Costa
Eduardo Almeida Marques-da-Silva
Ricardo Gonçalves
Sandra Aparecida Lima de Moura
Nelder Figueiredo Gontijo
Sydnei Magno da Silva
Marilene Suzan Marques Michalick
José Roberto Meyer-Fernandes
Roberto Paes de Carvalho
Silvia Reni Bortolin Uliana
Juliana Lopes Rangel Fietto
Luís Carlos Crocco Afonso
Leishmania metacyclogenesis is promoted in the absence of purines.
description Leishmania parasites, the causative agent of leishmaniasis, are transmitted through the bite of an infected sand fly. Leishmania parasites present two basic forms known as promastigote and amastigote which, respectively, parasitizes the vector and the mammalian hosts. Infection of the vertebrate host is dependent on the development, in the vector, of metacyclic promastigotes, however, little is known about the factors that trigger metacyclogenesis in Leishmania parasites. It has been generally stated that "stressful conditions" will lead to development of metacyclic forms, and with the exception of a few studies no detailed analysis of the molecular nature of the stress factor has been performed. Here we show that presence/absence of nucleosides, especially adenosine, controls metacyclogenesis both in vitro and in vivo. We found that addition of an adenosine-receptor antagonist to in vitro cultures of Leishmania amazonensis significantly increases metacyclogenesis, an effect that can be reversed by the presence of specific purine nucleosides or nucleobases. Furthermore, our results show that proliferation and metacyclogenesis are independently regulated and that addition of adenosine to culture medium is sufficient to recover proliferative characteristics for purified metacyclic promastigotes. More importantly, we show that metacyclogenesis was inhibited in sand flies infected with Leishmania infantum chagasi that were fed a mixture of sucrose and adenosine. Our results fill a gap in the life cycle of Leishmania parasites by demonstrating how metacyclogenesis, a key point in the propagation of the parasite to the mammalian host, can be controlled by the presence of specific purines.
format article
author Tiago Donatelli Serafim
Amanda Braga Figueiredo
Pedro Augusto Carvalho Costa
Eduardo Almeida Marques-da-Silva
Ricardo Gonçalves
Sandra Aparecida Lima de Moura
Nelder Figueiredo Gontijo
Sydnei Magno da Silva
Marilene Suzan Marques Michalick
José Roberto Meyer-Fernandes
Roberto Paes de Carvalho
Silvia Reni Bortolin Uliana
Juliana Lopes Rangel Fietto
Luís Carlos Crocco Afonso
author_facet Tiago Donatelli Serafim
Amanda Braga Figueiredo
Pedro Augusto Carvalho Costa
Eduardo Almeida Marques-da-Silva
Ricardo Gonçalves
Sandra Aparecida Lima de Moura
Nelder Figueiredo Gontijo
Sydnei Magno da Silva
Marilene Suzan Marques Michalick
José Roberto Meyer-Fernandes
Roberto Paes de Carvalho
Silvia Reni Bortolin Uliana
Juliana Lopes Rangel Fietto
Luís Carlos Crocco Afonso
author_sort Tiago Donatelli Serafim
title Leishmania metacyclogenesis is promoted in the absence of purines.
title_short Leishmania metacyclogenesis is promoted in the absence of purines.
title_full Leishmania metacyclogenesis is promoted in the absence of purines.
title_fullStr Leishmania metacyclogenesis is promoted in the absence of purines.
title_full_unstemmed Leishmania metacyclogenesis is promoted in the absence of purines.
title_sort leishmania metacyclogenesis is promoted in the absence of purines.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/5806430d98d24e3e98e9ff43318daddb
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