In the protozoan parasite Leishmania, most genes encoding for ribosomal proteins (RPs) are present as two or more copies in the genome. However, their untranslated regions (UTRs) are predominantly divergent and might be associated with a distinct regulation of the expression of paralogous genes. Herein, we investigated the expression profiles of two RPs (S16 and L13a) encoded by duplicated genes in Leishmania major.
View Article and Find Full Text PDFFront Cell Infect Microbiol
January 2022
Until 2015, loss-of-function studies to elucidate protein function in relied on gene disruption through homologous recombination. Then, the CRISPR/Cas9 revolution reached these protozoan parasites allowing efficient genome editing with one round of transfection. In addition, the development of LeishGEdit, a PCR-based toolkit for generating knockouts and tagged lines using CRISPR/Cas9, allowed a more straightforward and effective genome editing.
View Article and Find Full Text PDFSpecies-specific diagnosis still represents a challenge in leishmaniasis management, particularly in regions with multiple endemic species. In Brazil, seven species have been recognized as etiological agents of cutaneous leishmaniasis. The disease comprises complex clinical presentation patterns, classified as localized, diffuse, disseminated and mucocutaneous leishmaniasis.
View Article and Find Full Text PDFTreatment of visceral leishmaniasis in Brazil still relies on meglumine antimoniate, with less than ideal efficacy and safety, making new therapeutic tools an urgent need. The oral drug miltefosine was assayed in a phase II clinical trial in Brazil with cure rates lower than previously demonstrated in India. The present study investigated the susceptibility to miltefosine in 73 Brazilian strains of from different geographic regions, using intracellular amastigote and promastigote assays.
View Article and Find Full Text PDFThe Ros3 protein is a component of the MT-Ros3 transporter complex, considered as the main route of miltefosine entry in . clinical isolates presenting differences in miltefosine susceptibility and uptake were previously shown to differentially express . In this work, we showed that the gene copy number was increased in the isolate presenting the highest rates of miltefosine uptake and, thus, the highest susceptibility to this drug.
View Article and Find Full Text PDFIn Brazil, cutaneous leishmaniasis is caused predominantly by L. (V.) braziliensis.
View Article and Find Full Text PDFHsp70 is a cytoplasmic heat-shock protein, encoded by a multicopy tandemly repeated gene that has recently been gaining popularity as a valuable marker for typing Leishmania species. In this study, we used a previously described hsp70 PCR-RFLP method for identifying Brazilian Leishmania isolates. We identified two distinct L.
View Article and Find Full Text PDFThe aims of the present work were to test the effect of tamoxifen administered topically and the therapeutic efficacy of tamoxifen and pentavalent antimonial combinations in an experimental model of cutaneous leishmaniasis. BALB/c mice infected with a luciferase expressing line of Leishmania amazonensis were treated with topical tamoxifen in two different formulations (ethanol or oil-free cream) as monotherapy or in co-administration with pentavalent antimonial. Treatment efficacy was evaluated by lesion size and parasite burden, quantified through luminescence, at the end of treatment and 4 weeks later.
View Article and Find Full Text PDF() is the main causative species of tegumentary leishmaniasis in Brazil. In this study, we evaluated the susceptibility of 16 clinical isolates of () from different regions of Brazil to miltefosine in vitro. Half-maximal inhibitory concentrations of miltefosine varied from 22.
View Article and Find Full Text PDFBackground: Leishmania braziliensis is the most prevalent species isolated from patients displaying cutaneous and muco-cutaneous leishmaniasis in South America. However, there are difficulties for studying L. braziliensis pathogenesis or response to chemotherapy in vivo due to the natural resistance of most mouse strains to infection with these parasites.
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