| Author | Zabala-Peñafiel, Anabel | |
| Author | Cysne-Finkelstein, Lea | |
| Author | Silva, Fatima Conceição | |
| Author | Fagundes, Aline | |
| Author | Miranda, Luciana de Freitas Campos | |
| Author | Silva, Franklin Souza | |
| Author | Brandt, Artur A. M. L. | |
| Author | Lopes, Geovane Dias | |
| Author | Alves, Carlos Roberto | |
| Access date | 2022-06-30T20:56:32Z | |
| Available date | 2022-06-30T20:56:32Z | |
| Document date | 2022 | |
| Citation | Zabala-Peñafiel, Anabel et al. Novel Insights Into Leishmania (Viannia) braziliensis In Vitro Fitness Guided by Temperature Changes Along With Its Subtilisins and Oligopeptidase B. Frontiers in Cellular and Infection Microbiology, v. 12, Article 805106, p. 1 - 15, Apr. 2022. | pt_BR |
| ISSN | 2235-2988 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/53603 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Leishmania (Viannia) braziliensis | pt_BR |
| Subject in Portuguese | Características fenotípicas | pt_BR |
| Subject in Portuguese | Expressão genetica | pt_BR |
| Subject in Portuguese | Proteases de serina | pt_BR |
| Subject in Portuguese | Dinâmica molecular | pt_BR |
| Title | Novel Insights Into Leishmania (Viannia) braziliensis In Vitro Fitness Guided by Temperature Changes Along With Its Subtilisins and Oligopeptidase B | pt_BR |
| Type | Article | |
| DOI | 10.3389/fcimb.2022.805106 | |
| Abstract | Proteases are virulence factors with a recognized impact on the Leishmania spp. life cycle.
This study considers a set of analyses measuring phenotypic factors of L. (V.) braziliensis
clinical isolates as promastigotes growth curves, murine peritoneal macrophages
infection, inflammatory mediators production, and serine proteases gene expression
(subtilisin 13: S13, subtilisin 28: S28, oligopeptidase B: OPB) assessing these isolates’
fitness on in vitro conditions. Parasites had different behavior during the early growth
phase from day zero to day three, and all isolates reached the stationary growth phase
between days four and seven. Macrophages infection showed two tendencies, one of
decreased infection rate and number of parasites per macrophage (Infection Index <1000)
and another with a constant infection index (≥1400). TNF-a (≥10 pg/mL) detected in
infections by 75% of isolates, IL-6 (≥80 pg/mL) by 30% of isolates and low levels of NO
(≥0.01μM) in almost all infections. Gene expression showed higher values of S13 (≥2RQ) in
the intracellular amastigotes of all the isolates evaluated. On the contrary, S28 expression
was low (≤1RQ) in all isolates. OPB expression was different between promastigotes and
intracellular amastigotes, being significantly higher (≥2RQ) in the latter form of 58% of the
isolates. Predictive structural assays of S13 and OPB were performed to explore
temperature influence on gene expression and the encoded proteases. Gene
expression data is discussed based on in silico predictions of regulatory regions that
show plasticity in the linearity index of secondary structures of S13 and OPB 3’-
untranslated regions of mRNA, dependent on temperature changes. While hairpin
structures suggest an active region of mRNA for both genes above 26°C, pseudoknot
structure found in S13 is an indication of a particular profile of this gene at mammalian host temperatures (37°C). Furthermore, the predicted 3D structures are in accordance with the
influence of these temperatures on the catalytic site stability of both enzymes, favoring
their action over peptide substrates. Data gathered here suggest that L. (V.) braziliensis
serine proteases can be influenced by the temperature conditions affecting parasite
fitness throughout its life cycle. | 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 Imunoparasitologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. 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. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Universidade Iguaçu. Dom Rodrigo. Nova Iguaçu, Rio de Janeiro, Brasil. | pt_BR |
| Affilliation | Faculdade de Educação Tecnológica do Estado do Rio de Janeiro. Departamento de Computação e Sistemas. 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 Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Leishmania (Viannia) braziliensis | pt_BR |
| Subject | Phenotypic characteristics | pt_BR |
| Subject | Gene expression | pt_BR |
| Subject | Serine proteases | pt_BR |
| Subject | Molecular dynamics | pt_BR |
