Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum

Introduction Kala-azar is a disease resulting from infection by Leishmania donovani and Leishmania infantum. Most patients with the disease exhibit prolonged fever, wasting, anemia and hepatosplenomegaly without complications. However, some patients develop severe disease with hemorrhagic manifestat...

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Main Authors: Bruno Guedes Alcoforado Aguiar, Daniela Lemos Coelho, Dorcas Lamounier Costa, Betânia Paiva Drumond, Luiz Felipe Leomil Coelho, Lívio Carvalho Figueiredo, Danielle Alves Zacarias, Jailthon Carlos da Silva, Diego Peres Alonso, Paulo Eduardo Martins Ribolla, Edna Aoba Yassui Ishikawa, Samara Belchior Gaído, Carlos Henrique Nery Costa
Format: Article
Language:English
Published: Sociedade Brasileira de Medicina Tropical (SBMT) 2014-10-01
Series:Revista da Sociedade Brasileira de Medicina Tropical
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Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822014000500593&lng=en&tlng=en
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author Bruno Guedes Alcoforado Aguiar
Daniela Lemos Coelho
Dorcas Lamounier Costa
Betânia Paiva Drumond
Luiz Felipe Leomil Coelho
Lívio Carvalho Figueiredo
Danielle Alves Zacarias
Jailthon Carlos da Silva
Diego Peres Alonso
Paulo Eduardo Martins Ribolla
Edna Aoba Yassui Ishikawa
Samara Belchior Gaído
Carlos Henrique Nery Costa
author_facet Bruno Guedes Alcoforado Aguiar
Daniela Lemos Coelho
Dorcas Lamounier Costa
Betânia Paiva Drumond
Luiz Felipe Leomil Coelho
Lívio Carvalho Figueiredo
Danielle Alves Zacarias
Jailthon Carlos da Silva
Diego Peres Alonso
Paulo Eduardo Martins Ribolla
Edna Aoba Yassui Ishikawa
Samara Belchior Gaído
Carlos Henrique Nery Costa
author_sort Bruno Guedes Alcoforado Aguiar
collection DOAJ
description Introduction Kala-azar is a disease resulting from infection by Leishmania donovani and Leishmania infantum. Most patients with the disease exhibit prolonged fever, wasting, anemia and hepatosplenomegaly without complications. However, some patients develop severe disease with hemorrhagic manifestations, bacterial infections, jaundice, and edema dyspnea, among other symptoms, followed by death. Among the parasite molecules that might influence the disease severity are the macrophage migration inhibitory factor-like proteins (MIF1 and MIF2) and N-acetylglucosamine-1-phosphotransferase (NAGT), which act in the first step of protein N-glycosylation. This study aimed to determine whether MIF1, MIF2 and NAGT are virulence factors for severe kala-azar. Methods To determine the parasite genotype in kala-azar patients from Northeastern Brazil, we sequenced the NAGT genes of L. infantum from 68 patients as well as the MIF1 and MIF2 genes from 76 different subjects with diverse clinical manifestations. After polymerase chain reaction (PCR), the fragments were sequenced, followed by polymorphism identification. Results The nucleotide sequencing of the 144 amplicons revealed the absence of genetic variability of the NAGT, MIF1 and MIF2 genes between the isolates. The conservation of these genes suggests that the clinical variability of kala-azar does not depend upon these genes. Additionally, this conservation suggests that these genes may be critical for parasite survival. Conclusions NAGT, MIF1 and MIF2 do not alter the severity of kala-azar. NAGT, MIF1 and MIF2 are highly conserved among different isolates of identical species and exhibit potential for use in phylogenetic inferences or molecular diagnosis.
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spelling doaj.art-0339e28f5f8f4f6f808376c65540e6582022-12-22T03:28:52ZengSociedade Brasileira de Medicina Tropical (SBMT)Revista da Sociedade Brasileira de Medicina Tropical1678-98492014-10-0147559359810.1590/0037-8682-0183-2014S0037-86822014000500593Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantumBruno Guedes Alcoforado AguiarDaniela Lemos CoelhoDorcas Lamounier CostaBetânia Paiva DrumondLuiz Felipe Leomil CoelhoLívio Carvalho FigueiredoDanielle Alves ZacariasJailthon Carlos da SilvaDiego Peres AlonsoPaulo Eduardo Martins RibollaEdna Aoba Yassui IshikawaSamara Belchior GaídoCarlos Henrique Nery CostaIntroduction Kala-azar is a disease resulting from infection by Leishmania donovani and Leishmania infantum. Most patients with the disease exhibit prolonged fever, wasting, anemia and hepatosplenomegaly without complications. However, some patients develop severe disease with hemorrhagic manifestations, bacterial infections, jaundice, and edema dyspnea, among other symptoms, followed by death. Among the parasite molecules that might influence the disease severity are the macrophage migration inhibitory factor-like proteins (MIF1 and MIF2) and N-acetylglucosamine-1-phosphotransferase (NAGT), which act in the first step of protein N-glycosylation. This study aimed to determine whether MIF1, MIF2 and NAGT are virulence factors for severe kala-azar. Methods To determine the parasite genotype in kala-azar patients from Northeastern Brazil, we sequenced the NAGT genes of L. infantum from 68 patients as well as the MIF1 and MIF2 genes from 76 different subjects with diverse clinical manifestations. After polymerase chain reaction (PCR), the fragments were sequenced, followed by polymorphism identification. Results The nucleotide sequencing of the 144 amplicons revealed the absence of genetic variability of the NAGT, MIF1 and MIF2 genes between the isolates. The conservation of these genes suggests that the clinical variability of kala-azar does not depend upon these genes. Additionally, this conservation suggests that these genes may be critical for parasite survival. Conclusions NAGT, MIF1 and MIF2 do not alter the severity of kala-azar. NAGT, MIF1 and MIF2 are highly conserved among different isolates of identical species and exhibit potential for use in phylogenetic inferences or molecular diagnosis.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822014000500593&lng=en&tlng=enGenetic diversityKala-azarVisceral leishmaniasisMacrophage inhibition factorTropical diseasesSingle nucleotide polymorphism
spellingShingle Bruno Guedes Alcoforado Aguiar
Daniela Lemos Coelho
Dorcas Lamounier Costa
Betânia Paiva Drumond
Luiz Felipe Leomil Coelho
Lívio Carvalho Figueiredo
Danielle Alves Zacarias
Jailthon Carlos da Silva
Diego Peres Alonso
Paulo Eduardo Martins Ribolla
Edna Aoba Yassui Ishikawa
Samara Belchior Gaído
Carlos Henrique Nery Costa
Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum
Revista da Sociedade Brasileira de Medicina Tropical
Genetic diversity
Kala-azar
Visceral leishmaniasis
Macrophage inhibition factor
Tropical diseases
Single nucleotide polymorphism
title Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum
title_full Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum
title_fullStr Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum
title_full_unstemmed Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum
title_short Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum
title_sort genes that encodes nagt mif1 and mif2 are not virulence factors for kala azar caused by leishmania infantum
topic Genetic diversity
Kala-azar
Visceral leishmaniasis
Macrophage inhibition factor
Tropical diseases
Single nucleotide polymorphism
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822014000500593&lng=en&tlng=en
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