title: Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum.
abstract: BACKGROUND
  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.
authors.affiliation: Laboratório de Leishmanioses, Instituto de Doenças Tropicais Natan Portella, Universidade Federal do Piauí, Teresina, PI, Brasil.
authors.forename: Bruno Guedes Alcoforado
authors.initials: BG
authors.lastname: Aguiar
authors.affiliation: Laboratório de Leishmanioses, Instituto de Doenças Tropicais Natan Portella, Universidade Federal do Piauí, Teresina, PI, Brasil.
authors.forename: Daniela Lemos
authors.initials: DL
authors.lastname: Coelho
authors.affiliation: Laboratório de Leishmanioses, Instituto de Doenças Tropicais Natan Portella, Universidade Federal do Piauí, Teresina, PI, Brasil.
authors.forename: Dorcas Lamounier
authors.initials: DL
authors.lastname: Costa
authors.affiliation: Laboratório de Virologia, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brasil.
authors.forename: Betânia Paiva
authors.initials: BP
authors.lastname: Drumond
authors.affiliation: Laboratório de Vacinas, Universidade Federal de Alfenas, Alfenas, MG, Brasil.
authors.forename: Luiz Felipe Leomil
authors.initials: LF
authors.lastname: Coelho
authors.affiliation: Departamento de Agricultura, Centro de Ciências Humanas, Sociais e Agrárias, Universidade Federal da Paraíba, Bananeiras, PB, Brasil.
authors.forename: Lívio Carvalho
authors.initials: LC
authors.lastname: Figueiredo
authors.affiliation: Laboratório de Leishmanioses, Instituto de Doenças Tropicais Natan Portella, Universidade Federal do Piauí, Teresina, PI, Brasil.
authors.forename: Danielle Alves
authors.initials: DA
authors.lastname: Zacarias
authors.affiliation: Laboratório de Leishmanioses, Instituto de Doenças Tropicais Natan Portella, Universidade Federal do Piauí, Teresina, PI, Brasil.
authors.forename: Jailthon Carlos da
authors.initials: JC
authors.lastname: Silva
authors.affiliation: Departamento de Parasitologia, Instituto de Biociências, Universidade Estadual Paulista, São Paulo, SP, Brazil.
authors.forename: Diego Peres
authors.initials: DP
authors.lastname: Alonso
authors.affiliation: Departamento de Parasitologia, Instituto de Biociências, Universidade Estadual Paulista, São Paulo, SP, Brazil.
authors.forename: Paulo Eduardo Martins
authors.initials: PE
authors.lastname: Ribolla
authors.affiliation: Laboratório de Biologia Molecular, Núcleo de Medicina Tropical, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Edna Aoba Yassui
authors.initials: EA
authors.lastname: Ishikawa
authors.affiliation: Laboratório de Leishmanioses, Instituto de Doenças Tropicais Natan Portella, Universidade Federal do Piauí, Teresina, PI, Brasil.
authors.forename: Samara Belchior
authors.initials: SB
authors.lastname: Gaído
authors.affiliation: Laboratório de Leishmanioses, Instituto de Doenças Tropicais Natan Portella, Universidade Federal do Piauí, Teresina, PI, Brasil.
authors.forename: Carlos Henrique Nery
authors.initials: CH
authors.lastname: Costa
mesh_terms: D005838:Genotype; D006801:Humans; D018314:Leishmania infantum / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000469:parasitology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D037521:Virulence Factors; D017855:Transferases (Other Substituted Phosphate Groups); C030012:UDP-N-acetylglucosamine-lysosomal-enzyme-N-acetylglucosaminephosphotransferase