Recent advances in the taxonomy of the New World leishmanial parasites

Cupolillo, Elisa; Alves, Fábio; Brahim, Lúcia Regina; Naiff, M. F.; Pereira, Luiza de Oliveira Ramos; Oliveira-Neto, Manoel P.; Falqueto, Aline; Grimaldi, Gabriel

doi:10.1007/s004300100080

Cited by 18 publications

(11 citation statements)

References 23 publications

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“…The extensive reticulation suggests that recombination has occurred relatively frequently in L. braziliensis and L. guyanensis , as proposed by other authors [34]. As expected, L. braziliensis and L. naiffi presented higher within group average genetic distance values than L. guyanensis , even including L. shawi strains in the L. guyanensis group, corroborating previous studies on the genetic diversity of both L. braziliensis and L. naiffi [35], [36], [37], [38]. However, as far as we know, this is the first report of a high level of genetic diversity within L. lainsoni .…”

Section: Resultssupporting

confidence: 89%

New Insights on Taxonomy, Phylogeny and Population Genetics of Leishmania (Viannia) Parasites Based on Multilocus Sequence Analysis

et al. 2012

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The Leishmania genus comprises up to 35 species, some with status still under discussion. The multilocus sequence typing (MLST)—extensively used for bacteria—has been proposed for pathogenic trypanosomatids. For Leishmania, however, a detailed analysis and revision on the taxonomy is still required. We have partially sequenced four housekeeping genes—glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), mannose phosphate isomerase (MPI) and isocitrate dehydrogenase (ICD)—from 96 Leishmania (Viannia) strains and assessed their discriminatory typing capacity. The fragments had different degrees of diversity, and are thus suitable to be used in combination for intra- and inter-specific inferences. Species-specific single nucleotide polymorphisms were detected, but not for all species; ambiguous sites indicating heterozygosis were observed, as well as the putative homozygous donor. A large number of haplotypes were detected for each marker; for 6PGD a possible ancestral allele for L. (Viannia) was found. Maximum parsimony-based haplotype networks were built. Strains of different species, as identified by multilocus enzyme electrophoresis (MLEE), formed separated clusters in each network, with exceptions. NeighborNet of concatenated sequences confirmed species-specific clusters, suggesting recombination occurring in L. braziliensis and L. guyanensis. Phylogenetic analysis indicates L. lainsoni and L. naiffi as the most divergent species and does not support L. shawi as a distinct species, placing it in the L. guyanensis cluster. BURST analysis resulted in six clonal complexes (CC), corresponding to distinct species. The L. braziliensis strains evaluated correspond to one widely geographically distributed CC and another restricted to one endemic area. This study demonstrates the value of systematic multilocus sequence analysis (MLSA) for determining intra- and inter-species relationships and presents an approach to validate the species status of some entities. Furthermore, it contributes to the phylogeny of L. (Viannia) and might be helpful for epidemiological and population genetics analysis based on haplotype/diplotype determinations and inferences.

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Section: Resultssupporting

confidence: 89%

New Insights on Taxonomy, Phylogeny and Population Genetics of Leishmania (Viannia) Parasites Based on Multilocus Sequence Analysis

et al. 2012

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“…Thus, they may represent at least two nonsympatric lineages of this parasite. As it was proposed by Cupolillo (9,11,13), the polymorphism observed could be related to the great number of sand fly vectors and animal reservoir hosts of the rain forests, especially in the southern part of the country. This particular Leishmania species is said not to be very polymorphic; however, to our knowledge, no large-scale study on L. The possibility of mixed infections has been previously reported (23,29,31,49).…”

Section: Discussionmentioning

confidence: 74%

Molecular Epidemiology of Leishmania ( Viannia ) guyanensis in French Guiana

et al. 2006

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Little information is available about the genetic variability of Leishmania populations and the possible correlations with ecoepidemiological features of leishmaniases. The present study was carried out in French Guiana, a country where cutaneous leishmaniases (CL) are endemic over the whole territory. The genetic polymorphism of a nuclear sequence encompassing the end of the ribosomal small subunit and the internal transcribed spacer 1 of 265 isolates from patients with CL was examined by restriction fragment length polymorphism analysis. Genotypes based on the fingerprinting phenetic integration were compared to epidemiological, clinical, and geographical data. In agreement with previous reports, five different Leishmania species were identified, but Leishmania (Viannia) guyanensis represented 95.8% of the samples. Two distinct L. (V.) guyanensis populations were found to originate in two ecologically characterized regions. Higher lesional parasite densities and the need for additional treatments were significantly linked to genotype group I. Parasites of genotype group II were more likely to cause chronic and disseminated cutaneous forms in patients. L. (V.) guyanensis was previously said not to be very polymorphic; however, the present analysis resulted in a significant degree of discrimination among L. (V.) guyanensis isolates from diverse ecological areas and with different clinical implications.In the highly biodiversified region of the New World (NW) that encompasses the northern Amazon Basin and the Guiana Shield, at least seven named species belonging to the Leishmania genus coexist with often overlapping hosts and vectors (39). American visceral leishmaniases due to Leishmania (Leishmania) infantum are found there, but cases of cutaneous leishmaniases (CL) are far more numerous. Human cutaneous infections may be unapparent; however, many of the Leishmania parasites are able to produce a spectrum of diseases rather than a single clinical form. Cases reported in that region range from localized and diffuse cutaneous forms to mucocutaneous leishmaniases. They are now being reported in areas where leishmaniases had previously not been endemic (2, 17): increasing risk factors related to natural and especially manmade environmental changes are making leishmaniases a growing public health concern in this particular region. However, little information is available about the genetic variability of parasite populations and the possible correlation with ecoepidemiological features of the diseases. The present study was carried out in French Guiana, a country where CL are endemic over the whole territory (incidence of 0. 2% between 1979 and 2000 [6, 14]). The genetic polymorphism of a nuclear sequence encompassing the end of the ribosomal small subunit (SSU) and the internal transcribed spacer 1 (ITS1) of 265 samples from patients with CL was examined by restriction fragment length polymorphism (RFLP) analysis. Genotypes based on the fingerprinting phenetic integration were then compared to epidemiological, clin...

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“…Taxonomic studies of field Leishmania isolates indicate a tremendous diversity within this genus [34], and genetic diversity may have a direct impact on relevant properties of the organisms, including distinct clinical manifestations and drug susceptibility [35]. So, it is not surprising that the effect of HIV PIs on Leishmania species responsible for visceral or mucocutaneous leishmaniasis seems to be very distinct.…”

Section: Discussionmentioning

confidence: 99%

HIV Aspartyl Peptidase Inhibitors Interfere with Cellular Proliferation, Ultrastructure and Macrophage Infection of Leishmania amazonensis

et al. 2009

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Background Leishmania is the etiologic agent of leishmanisais, a protozoan disease whose pathogenic events are not well understood. Current therapy is suboptimal due to toxicity of the available therapeutic agents and the emergence of drug resistance. Compounding these problems is the increase in the number of cases of Leishmania-HIV coinfection, due to the overlap between the AIDS epidemic and leishmaniasis.Methodology/Principal FindingsIn the present report, we have investigated the effect of HIV aspartyl peptidase inhibitors (PIs) on the Leishmania amazonensis proliferation, ultrastructure, interaction with macrophage cells and expression of classical peptidases which are directly involved in the Leishmania pathogenesis. All the HIV PIs impaired parasite growth in a dose-dependent fashion, especially nelfinavir and lopinavir. HIV PIs treatment caused profound changes in the leishmania ultrastructure as shown by transmission electron microscopy, including cytoplasm shrinking, increase in the number of lipid inclusions and some cells presenting the nucleus closely wrapped by endoplasmic reticulum resembling an autophagic process, as well as chromatin condensation which is suggestive of apoptotic death. The hydrolysis of HIV peptidase substrate by L. amazonensis extract was inhibited by pepstatin and HIV PIs, suggesting that an aspartyl peptidase may be the intracellular target of the inhibitors. The treatment with HIV PIs of either the promastigote forms preceding the interaction with macrophage cells or the amastigote forms inside macrophages drastically reduced the association indexes. Despite all these beneficial effects, the HIV PIs induced an increase in the expression of cysteine peptidase b (cpb) and the metallopeptidase gp63, two well-known virulence factors expressed by Leishmania spp.Conclusions/SignificanceIn the face of leishmaniasis/HIV overlap, it is critical to further comprehend the sophisticated interplays among Leishmania, HIV and macrophages. In addition, there are many unresolved questions related to the management of Leishmania-HIV-coinfected patients. For instance, the efficacy of therapy aimed at controlling each pathogen in coinfected individuals remains largely undefined. The results presented herein add new in vitro insight into the wide spectrum efficacy of HIV PIs and suggest that additional studies about the synergistic effects of classical antileishmanial compounds and HIV PIs in macrophages coinfected with Leishmania and HIV-1 should be performed.

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Recent advances in the taxonomy of the New World leishmanial parasites

Cited by 18 publications

References 23 publications

New Insights on Taxonomy, Phylogeny and Population Genetics of Leishmania (Viannia) Parasites Based on Multilocus Sequence Analysis

New Insights on Taxonomy, Phylogeny and Population Genetics of Leishmania (Viannia) Parasites Based on Multilocus Sequence Analysis

Molecular Epidemiology of Leishmania ( Viannia ) guyanensis in French Guiana

HIV Aspartyl Peptidase Inhibitors Interfere with Cellular Proliferation, Ultrastructure and Macrophage Infection of Leishmania amazonensis

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