title: Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil.
abstract: The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, approximately 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.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, SP, Brazil.
authors.forename: Julio César
authors.initials: JC
authors.lastname: Carranza
authors.forename: Helder M S
authors.initials: HM
authors.lastname: Valadares
authors.forename: Daniella A
authors.initials: DA
authors.lastname: D'Avila
authors.forename: Rodrigo P
authors.initials: RP
authors.lastname: Baptista
authors.forename: Margoth
authors.initials: M
authors.lastname: Moreno
authors.forename: Lúcia M C
authors.initials: LM
authors.lastname: Galvão
authors.forename: Egler
authors.initials: E
authors.lastname: Chiari
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Sturm
authors.forename: Eliane D
authors.initials: ED
authors.lastname: Gontijo
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Macedo
authors.forename: Bianca
authors.initials: B
authors.lastname: Zingales
mesh_terms: D000818:Animals; D001938:Brazil / Q000453:epidemiology; D002598:Chagas Cardiomyopathy / Q000453:epidemiology / Q000235:genetics* / Q000469:parasitology; D014355:Chagas Disease / Q000453:epidemiology / Q000235:genetics* / Q000469:parasitology; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D008565:Membrane Proteins; C107339:ND7 protein, Protozoa; D015800:Protozoan Proteins; D009245:NADH Dehydrogenase