Antimony insensitivity might occur in a stepwise fashion (first to SbV and then to SbIII). Our data question the definition of true parasite resistance to antimonials. Further studies of treatment efficacy should apply standardized protocols and definitions and should also consider host factors.
To make reliable interpretations about evolutionary relationships between Trypanosoma rangeli lineages and their insect vectors (triatomine bugs of the genus Rhodnius ) and, thus, about the determinant factors of lineage segregation within T. rangeli , we compared phylogenies of parasite isolates and vector species. Sixty-one T. rangeli isolates from invertebrate and vertebrate hosts were initially evaluated in terms of polymorphism of the spliced-leader gene (SL). Further analysis based on SL and SSUrRNA sequences from 33 selected isolates, representative of the overall phylogenetic diversity and geographical range of T. rangeli , supported four phylogenetic lineages within this species. By comparing the phylogeny of Rhodnius species with that inferred for T. rangeli isolates and through analysis of the geographical range of the isolates, we showed that there is a very significant overlap in the distribution of Rhodnius species and T. rangeli lineages. Congruence between phylogeographical analysis of both T. rangeli lineages and complexes of Rhodnius species are consistent with the hypothesis of a long coexistence of parasites and their vectors, with lineage divergence associated with sympatric species of Rhodnius apparently without association with particular vertebrate hosts. Separation of T. rangeli isolates from vectors of distinct complexes living in sympatry favours the absence of gene flow between the lineages and suggests evolution of T. rangeli lineages in independent transmission cycles, probably associated to specific Rhodnius spp. ecotopes. A polymerase chain reaction assay based on SL intergenic sequences was developed for simultaneous identification and lineage genotyping of T. rangeli in epidemiological surveys.Keywords : evolution, phylogeography, Rhodnius , ribosomal gene, spliced-leader gene, Trypanosoma rangeli
Received 4 March 2007; revision received 4 March 2007; accepted 12 April 2007
IntroductionThe family Trypanosomatidae (Euglenozoa: Kinetoplastida) comprises eight genera of protozoan parasites of vertebrates, invertebrates and plants. The genus Trypanosoma harbours parasites of all vertebrate classes and the life cycle of these parasites involves alternation between two hosts: vertebrates and diverse haematophagous invertebrates (vectors). This genus includes only three Trypanosoma species that infect man: T. cruzi and T. rangeli in Latin America and T. brucei in Africa (Stevens et al . 2001).Trypanosoma rangeli infects humans, and domestic, and sylvatic mammals from Central America to southern South America sharing with T. cruzi the same mammalian hosts and triatomine vectors in overlapping areas. A high & Saravia 1999;Guhl & Vallejo 2003). In Brazil, only three human cases have been reported in Amazonia (Coura et al . 1996), whereas infection of sylvatic mammals and triatomines is very common in this region (Miles et al . 1983; Maia da Silva et al . 2004a, b) and has also been reported in southern, southeastern and central regions (Steindel et al . 1991;Ramirez et al . 2002...
Leishmaniasis is a disease with ample clinical spectrum and epidemiological diversity and is considered a major public health problem. This article presents an overview of the transmission cycles, host-parasite interactions, clinical, histological and immunological aspects, diagnosis and treatment of various forms of the human disease.
The conserved, nonantigenic, nonimmunogenic malaria Merozoite Surface Protein-2 peptide 1, having high affinity for red blood cells, was rendered immunogenic and protective in Aotus monkeys by specifically changing some critical residues. The NMR structure revealed a switch from classical type III' into distorted III' and III beta turns in the protective peptides. These changes may lead to a better fit into the Aotus MHC class II human HLA-DRbeta1 12 molecule equivalent, thus activating the immune system.
ATP-dependent proteases of the AAA+ family, including Escherichia coli ClpXP and the eukaryotic proteasome, contribute to maintenance of cellular proteostasis. ClpXP unfolds and translocates its substrates into an internal degradation chamber using cycles of alternating dwell and burst phases. The ClpX motor performs chemical transformations during the dwell and translocates the substrate in 1-4 nm increments during the burst, but what processes occur during these phases remains unknown. Here we characterize the complete mechanochemical cycle of ClpXP, showing that ADP release and ATP binding happen non-sequentially during the dwell, while ATP hydrolysis and phosphate release occur during the burst. The highly-conserved translocating loops within the ClpX pore are evolutionarily optimized to maximize motor power generation, the coupling between chemical and mechanical tasks, and the efficiency of protein processing. Conformational resetting of these loops between consecutive bursts seems to determine ADP release from individual ATPase subunits and the overall duration of the motor's cycle.
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