Expresión diferencial de proteínas en Leishmania (Viannia) panamensis asociadas con mecanismos de resistencia a antimoniato de meglumina

Sanchez, Ronald Guillermo Peláez; Muskus, Carlos; Cuervo, Patrícia; Marín-Villa, Marcel

doi:10.7705/biomedica.v32i3.392

Cited by 5 publications

(1 citation statement)

References 39 publications

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“…demonstrated prominent expression profiles of HSP83, heat shock protein-60 (HSP60), and HSP70 in the resistant cell lines of both L. braziliensis and L. infantum chagasi , particularly the HSP70 equivalents, having boosted in both the cytoplasm and the mitochondria of the L. infantum chagasi lines (Matrangolo et al ., 2013). HSP70 and HSP83 were reported to be overexpressed in the membrane-enriched fraction of the SAG-resistant L. donovani clinical isolates (Kumar et al ., 2010), and in the meantime, the increased expression pattern of HSP60 and HSP70 has been observed in relation to Sb-resistant mechanisms in L. (Viannia) panamensis (Peláez et al ., 2012). The substantial abundance of HSP70 in in vitro selected Sb-resistant Leishmania of both amastigotes and promastigotes, and the corresponding revertant cells in the absence of drug pressure, could be suggestive of the stability and functional significance of this protein in Sb-resistant Leishmania (Brochu et al ., 2004).…”

Section: Heat Shock Proteinsmentioning

confidence: 99%

Antimony resistance and gene expression inLeishmania: spotlight on molecular and proteomic aspects

Madusanka,

Karunaweera,

Silva

et al. 2023

Parasitology

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Leishmaniasis is a vector-borne parasitic disease caused by Leishmania parasites with a spectrum of clinical manifestations, ranging from skin lesions to severe visceral complications. Treatment of this infection has been extremely challenging with the concurrent emergence of drug resistance. The differential gene expression and the discrepancies in protein functions contribute to the appearance of 2 distinct phenotypes: resistant and sensitive, but the current diagnostic tools fail to differentiate between them. The identification of gene expression patterns and molecular mechanisms coupled with antimony (Sb) resistance can be leveraged to prompt diagnosis and select the most effective treatment methods. The present study attempts to use comparative expression of Sb resistance-associated genes in resistant and sensitive Leishmania, to disclose their relative abundance in clinical or in vitro selected isolates to gain an understanding of the molecular mechanisms of Sb response/resistance. Data suggest that the analysis of resistance gene expression would verify the Sb resistance or susceptibility only to a certain extent; however, none of the individual expression patterns of the studied genes was diagnostic as a biomarker of Sb response of Leishmania. The findings highlighted will be useful in bridging the knowledge gap and discovering innovative diagnostic tools and novel therapeutic targets.

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Section: Heat Shock Proteinsmentioning

confidence: 99%

Antimony resistance and gene expression inLeishmania: spotlight on molecular and proteomic aspects

Madusanka,

Karunaweera,

Silva

et al. 2023

Parasitology

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Phosphoproteomic analysis of wild‐type and antimony‐resistant Leishmania braziliensis lines by 2D‐DIGE technology

Moreira¹,

Pescher

Laurent

et al. 2015

Proteomics

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Protein phosphorylation is one of the most studied post-translational modifications that is involved in different cellular events in Leishmania. In this study, we performed a comparative phosphoproteomics analysis of potassium antimonyl tartrate (SbIII)-resistant and -susceptible lines of Leishmania braziliensis using a 2D-DIGE approach followed by MS. In order to investigate the differential phosphoprotein abundance associated with the drug-induced stress response and SbIII-resistance mechanisms, we compared nontreated and SbIII-treated samples of each line. Pair wise comparisons revealed a total of 116 spots that showed a statistically significant difference in phosphoprotein abundance, including 11 and 34 spots specifically correlated with drug treatment and resistance, respectively. We identified 48 different proteins distributed into seven biological process categories. The category "protein folding/chaperones and stress response" is mainly implicated in response to SbIII treatment, while the categories "antioxidant/detoxification," "metabolic process," "RNA/DNA processing," and "protein biosynthesis" are modulated in the case of antimony resistance. Multiple sequence alignments were performed to validate the conservation of phosphorylated residues in nine proteins identified here. Western blot assays were carried out to validate the quantitative phosphoproteome analysis. The results revealed differential expression level of three phosphoproteins in the lines analyzed. This novel study allowed us to profile the L. braziliensis phosphoproteome, identifying several potential candidates for biochemical or signaling networks associated with antimony resistance phenotype in this parasite.

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The Role of Proteomics in the Study of Drug Resistance

Sabóia-Vahia

Jesus

Cuervo

2018

Drug Resistance in Leishmania Parasites

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Expresión diferencial de proteínas en Leishmania (Viannia) panamensis asociadas con mecanismos de resistencia a antimoniato de meglumina

Cited by 5 publications

References 39 publications

Antimony resistance and gene expression inLeishmania: spotlight on molecular and proteomic aspects

Antimony resistance and gene expression inLeishmania: spotlight on molecular and proteomic aspects

Phosphoproteomic analysis of wild‐type and antimony‐resistant Leishmania braziliensis lines by 2D‐DIGE technology

The Role of Proteomics in the Study of Drug Resistance

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