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Prolyl Oligopeptidase From Leishmania infantum : Biochemical Characterization and Involvement in Macrophage Infection.

التفاصيل البيبلوغرافية
العنوان: Prolyl Oligopeptidase From Leishmania infantum : Biochemical Characterization and Involvement in Macrophage Infection.
المؤلفون: Lasse C; Pathogen-Host Interface Laboratory, Department of Cell Biology, University of Brasília, Brasília, Brazil., Azevedo CS; Pathogen-Host Interface Laboratory, Department of Cell Biology, University of Brasília, Brasília, Brazil.; UMR 7245 MCAM, Musèum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Paris, France., de Araújo CN; Pathogen-Host Interface Laboratory, Department of Cell Biology, University of Brasília, Brasília, Brazil.; Faculty of Ceilandia, University of Brasília, Brasília, Brazil., Motta FN; Pathogen-Host Interface Laboratory, Department of Cell Biology, University of Brasília, Brasília, Brazil.; Faculty of Ceilandia, University of Brasília, Brasília, Brazil., Andrade MA; Pathogen-Host Interface Laboratory, Department of Cell Biology, University of Brasília, Brasília, Brazil.; UMR 7245 MCAM, Musèum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Paris, France., Rocha AP; Pathogen-Host Interface Laboratory, Department of Cell Biology, University of Brasília, Brasília, Brazil., Sampaio I; Pathogen-Host Interface Laboratory, Department of Cell Biology, University of Brasília, Brasília, Brazil., Charneau S; Laboratory of Protein Chemistry and Biochemistry, Department of Cell Biology, University of Brasília, Brasília, Brazil., Gèze M; UMR 7245 MCAM, Musèum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Paris, France.; CeMIM, Musèum National d'Histoire Naturelle, Paris, France., Grellier P; UMR 7245 MCAM, Musèum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Paris, France., Santana JM; Pathogen-Host Interface Laboratory, Department of Cell Biology, University of Brasília, Brasília, Brazil., Bastos IMD; Pathogen-Host Interface Laboratory, Department of Cell Biology, University of Brasília, Brasília, Brazil.
المصدر: Frontiers in microbiology [Front Microbiol] 2020 May 28; Vol. 11, pp. 1060. Date of Electronic Publication: 2020 May 28 (Print Publication: 2020).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101548977 Publication Model: eCollection Cited Medium: Print ISSN: 1664-302X (Print) Linking ISSN: 1664302X NLM ISO Abbreviation: Front Microbiol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne : Frontiers Research Foundation
مستخلص: Leishmania infantum is a flagellated protozoan and one of the main causative agents of visceral leishmaniasis. This disease usually affects the human reticuloendothelial system, can cause death and available therapies may lead to serious side effects. Since it is a neglected tropical disease, the incentives for the development of new drugs are insufficient. It is important to know Leishmania virulence factors that contribute most to the disease in order to develop drugs. In the present work, we have produced L. infantum prolyl oligopeptidase (rPOPLi) in Escherichia coli , and investigated its biochemical properties as well as the effect of POP inhibitors on its enzymatic activity and on the inhibition of the macrophage infection by L. infantum . The optimal activity occurred at pH 7.5 and 37°C in the presence of DTT, the latter increased rPOPLi catalytic efficiency 5-fold on the substrate N- Suc-Gly-Pro-Leu-Gly-Pro-AMC. The enzyme was inhibited by TPCK, TLCK and by two POP specific inhibitors, Z-Pro-prolinal (ZPP, IC 50 4.2 nM) and S17092 (IC 50 3.5 nM). Besides being a cytoplasmic enzyme, POPLi is also found in punctuate structures within the parasite cytoplasm or associated with the parasite plasma membrane in amastigotes and promastigotes, respectively. Interestingly, S17092 and ZPP prevented parasite invasion in murine macrophages, supporting the involvement of POPLi in the invasive process of L. infantum. These data suggest POPLi as a virulence factor that offers potential as a target for designing new antileishmanial drugs.
(Copyright © 2020 Lasse, Azevedo, de Araújo, Motta, Andrade, Rocha, Sampaio, Charneau, Gèze, Grellier, Santana and Bastos.)
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فهرسة مساهمة: Keywords: POPLi; drug target; leishmaniasis; protease; virulence factor
تواريخ الأحداث: Date Created: 20200618 Latest Revision: 20200928
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7271538
DOI: 10.3389/fmicb.2020.01060
PMID: 32547514
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-302X
DOI:10.3389/fmicb.2020.01060