| Author | Zabala‑Peñafel, Anabel | |
| Author | Lopes, Geovane Dias | |
| Author | Cysne‑Finkelstein, Léa | |
| Author | Silva, Fátima Conceição | |
| Author | Miranda, Luciana de Freitas Campos | |
| Author | Fagundes, Aline | |
| Author | Schubach, Armando de Oliveria | |
| Author | Pimentel, Maria Inês Fernandes | |
| Author | Silva, Franklin Souza | |
| Author | Machado, Lucas de Almeida | |
| Author | Alves, Carlos Roberto | |
| Access date | 2021-07-14T14:02:56Z | |
| Available date | 2021-07-14T14:02:56Z | |
| Document date | 2021 | |
| Citation | ZABALA-PENAFIEL, Anabel et al. Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony. Scientific Reports, v. 11, 14234, 11 p, 2021. | pt_BR |
| ISSN | 2045-2322 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/48232 | |
| Language | eng | pt_BR |
| Publisher | Nature | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Perfis de proteases serinos | pt_BR |
| Subject in Portuguese | Leishmania (Viannia) braziliensis | pt_BR |
| Subject in Portuguese | Suscetibilidades | pt_BR |
| Subject in Portuguese | Antimônio | pt_BR |
| Title | Serine proteases profles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony | pt_BR |
| Type | Article | |
| Abstract | Glucantime (SbV) is the frst-line treatment against American Tegumentary Leishmaniasis. Resistance
cases to this drug have been reported and related to host characteristics and parasite phenotypes.
In this study, 12 Leishmania (Viannia) braziliensis isolates from patients that presented clinical cure
(Responders—R) and relapse or therapeutic failure (Non-responders—NR) after treatment with
antimony, were analyzed. These parasites were assessed by in vitro susceptibility to SbIII and SbV,
serine proteases activity measured with substrate (z-FR-AMC) and specifc inhibitors (TLCK, AEBSF
and PMSF). In vitro susceptibility of axenic amastigotes to SbIII showed a signifcant diference
between R and NR groups. The protease assays showed that TLCK inhibited almost 100% of activity
in both axenic amastigotes and promastigotes while AEBSF inhibited around 70%, and PMSF
showed lower inhibition of some isolates. Principal component and clustering analysis performed
with these data yielded one homogeneous cluster with only NR isolates and three heterogeneous
clusters with R and NR isolates. Additionally, diferential expression of subtilisins (LbrM.13.0860 and
LbrM.28.2570) and TXNPx (LbrM.15.1080) was evaluated in promastigotes and axenic amastigotes
from both groups. The results showed a higher expression of LbrM.13.0860 and LbrM.15.1080 genes
in axenic amastigotes, while LbrM.28.2570 gene had the lowest expression in all isolates, regardless
of the parasite form. The data presented here show a phenotypic heterogeneity among the parasites,
suggesting that exploration of in vitro phenotypes based on SbIII and serine proteases profles can aid
in the characterization of L. (V.) braziliensis clinical isolates. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunopatologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunopatologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Serine proteases profiles | pt_BR |
| Subject | Leishmania (Viannia) braziliensis | pt_BR |
| Subject | Susceptibilities | pt_BR |
| Subject | Antimony | pt_BR |
| e-ISSN | 10.1038/s41598-021-93665-z | |
