TY - JOUR
T1 - Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil
AU - Carranza, Julio César
AU - Valadares, Helder M.S.
AU - D'Ávila, Daniella A.
AU - Baptista, Rodrigo P.
AU - Moreno, Margoth
AU - Galvão, Lúcia M.C.
AU - Chiari, Egler
AU - Sturm, Nancy R.
AU - Gontijo, Eliane D.
AU - Macedo, Andrea M.
AU - Zingales, Bianca
N1 - Funding Information:
We thank Marcelo N. Silva for technical assistance. This work was supported by grants of Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Ministério de Ciência e Tecnologia/Conselho Nacional de Desenvolvimento Científico e Tecnológico/Ministério da Saúde (MCT/CNPq/MS-SCTIE-DECIT-Edital de Doenças Negligenciadas) (B.Z.) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) (A.M.M.). N.S. received support from NIH Grant AI056034. J.C.C. was the recipient of a graduation fellowship from the Universidad del Tolima (Ibagué, Colombia) and Instituto Colombiano Francisco José de Caldas (COLCIENCIAS).
PY - 2009/7/15
Y1 - 2009/7/15
N2 - The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, ∼3% of them develop lesions in the heart or gastrointestinal tract. Cardiomyopathy (CCHD) is the most severe manifestation of Chagas disease. The factors that determine the outcome of the infection are unknown, but certainly depend on complex interactions amongst the genetic make-up of the parasite, the host immunogenetic background and environment. In a previous study we verified that the maxicircle gene NADH dehydrogenase (mitochondrial complex I) subunit 7 (ND7) from IF isolates had a 455 bp deletion compared with the wild type (WT) ND7 gene from CCHD strains. We proposed that ND7 could constitute a valuable target for PCR assays in the differential diagnosis of the infective strain. In the present study we evaluated this hypothesis by examination of ND7 structure in parasites from 75 patients with defined pathologies, from Southeast Brazil. We also analysed the structure of additional mitochondrial genes (ND4/CR4, COIII and COII) since the maxicircle is used for clustering Trypanosoma cruzi strains into three clades/haplogroups. We conclude that maxicircle genes do not discriminate parasite populations which induce IF or CCHD forms. Interestingly, the great majority of the analysed isolates belong to T. cruzi II (discrete typing unit, (DTU) IIb) genotype. This scenario is at variance with the prevalence of hybrid (DTU IId) human isolates in Bolivia, Chile and Argentina. The distribution of WT and deleted ND7 and ND4 genes in T. cruzi strains suggests that mutations in the two genes occurred in different ancestrals in the T. cruzi II cluster, allowing the identification of at least three mitochondrial sub-lineages within this group. The observation that T. cruzi strains accumulate mutations in several genes coding for complex I subunits favours the hypothesis that complex I may have a limited activity in this parasite.
AB - The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, ∼3% of them develop lesions in the heart or gastrointestinal tract. Cardiomyopathy (CCHD) is the most severe manifestation of Chagas disease. The factors that determine the outcome of the infection are unknown, but certainly depend on complex interactions amongst the genetic make-up of the parasite, the host immunogenetic background and environment. In a previous study we verified that the maxicircle gene NADH dehydrogenase (mitochondrial complex I) subunit 7 (ND7) from IF isolates had a 455 bp deletion compared with the wild type (WT) ND7 gene from CCHD strains. We proposed that ND7 could constitute a valuable target for PCR assays in the differential diagnosis of the infective strain. In the present study we evaluated this hypothesis by examination of ND7 structure in parasites from 75 patients with defined pathologies, from Southeast Brazil. We also analysed the structure of additional mitochondrial genes (ND4/CR4, COIII and COII) since the maxicircle is used for clustering Trypanosoma cruzi strains into three clades/haplogroups. We conclude that maxicircle genes do not discriminate parasite populations which induce IF or CCHD forms. Interestingly, the great majority of the analysed isolates belong to T. cruzi II (discrete typing unit, (DTU) IIb) genotype. This scenario is at variance with the prevalence of hybrid (DTU IId) human isolates in Bolivia, Chile and Argentina. The distribution of WT and deleted ND7 and ND4 genes in T. cruzi strains suggests that mutations in the two genes occurred in different ancestrals in the T. cruzi II cluster, allowing the identification of at least three mitochondrial sub-lineages within this group. The observation that T. cruzi strains accumulate mutations in several genes coding for complex I subunits favours the hypothesis that complex I may have a limited activity in this parasite.
KW - Chagas disease
KW - Clinical presentations
KW - Microsatellites
KW - Mitochondrial complex I
KW - NADH dehydrogenase subunit 7
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U2 - 10.1016/j.ijpara.2009.01.009
DO - 10.1016/j.ijpara.2009.01.009
M3 - Article
C2 - 19504756
AN - SCOPUS:67349109158
SN - 0020-7519
VL - 39
SP - 963
EP - 973
JO - International Journal for Parasitology
JF - International Journal for Parasitology
IS - 9
ER -