Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony

Abstract Glucantime (SbV) is the first-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 cl...

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Autores principales:	Anabel Zabala-Peñafiel, Geovane Dias-Lopes, Léa Cysne-Finkelstein, Fátima Conceição-Silva, Luciana de Freitas Campos Miranda, Aline Fagundes, Armando de Oliveira Schubach, Maria Inês Fernandes Pimentel, Franklin Souza-Silva, Lucas de Almeida Machado, Carlos Roberto Alves
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c189acbd39044fa790974bc4c3479a94
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spelling	oai:doaj.org-article:c189acbd39044fa790974bc4c3479a942021-12-02T16:24:49ZSerine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony10.1038/s41598-021-93665-z2045-2322https://doaj.org/article/c189acbd39044fa790974bc4c3479a942021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93665-zhttps://doaj.org/toc/2045-2322Abstract Glucantime (SbV) is the first-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 specific inhibitors (TLCK, AEBSF and PMSF). In vitro susceptibility of axenic amastigotes to SbIII showed a significant difference 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, differential 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 profiles can aid in the characterization of L. (V.) braziliensis clinical isolates.Anabel Zabala-PeñafielGeovane Dias-LopesLéa Cysne-FinkelsteinFátima Conceição-SilvaLuciana de Freitas Campos MirandaAline FagundesArmando de Oliveira SchubachMaria Inês Fernandes PimentelFranklin Souza-SilvaLucas de Almeida MachadoCarlos Roberto AlvesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anabel Zabala-Peñafiel Geovane Dias-Lopes Léa Cysne-Finkelstein Fátima Conceição-Silva Luciana de Freitas Campos Miranda Aline Fagundes Armando de Oliveira Schubach Maria Inês Fernandes Pimentel Franklin Souza-Silva Lucas de Almeida Machado Carlos Roberto Alves Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony
description	Abstract Glucantime (SbV) is the first-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 specific inhibitors (TLCK, AEBSF and PMSF). In vitro susceptibility of axenic amastigotes to SbIII showed a significant difference 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, differential 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 profiles can aid in the characterization of L. (V.) braziliensis clinical isolates.
format	article
author	Anabel Zabala-Peñafiel Geovane Dias-Lopes Léa Cysne-Finkelstein Fátima Conceição-Silva Luciana de Freitas Campos Miranda Aline Fagundes Armando de Oliveira Schubach Maria Inês Fernandes Pimentel Franklin Souza-Silva Lucas de Almeida Machado Carlos Roberto Alves
author_facet	Anabel Zabala-Peñafiel Geovane Dias-Lopes Léa Cysne-Finkelstein Fátima Conceição-Silva Luciana de Freitas Campos Miranda Aline Fagundes Armando de Oliveira Schubach Maria Inês Fernandes Pimentel Franklin Souza-Silva Lucas de Almeida Machado Carlos Roberto Alves
author_sort	Anabel Zabala-Peñafiel
title	Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony
title_short	Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony
title_full	Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony
title_fullStr	Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony
title_full_unstemmed	Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony
title_sort	serine proteases profiles of leishmania (viannia) braziliensis clinical isolates with distinct susceptibilities to antimony
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c189acbd39044fa790974bc4c3479a94
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Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony

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