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LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro

Protein phosphorylation/dephosphorylation is an important regulatory mechanism that controls many key physiological processes. Numerous pathogens successfully use kinases and phosphatases to internalize, replicate, and survive, modifying the host′s phosphorylation profile or signal transduction path...

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Autores principales: Kraeva, Natalya, Leštinová, Tereza, Ishemgulova, Aygul, Majerová, Karolina, Butenko, Anzhelika, Vaselek, Slavica, Bespyatykh, Julia, Charyyeva, Arzuv, Spitzová, Tatiana, Kostygov, Alexei Yu., Lukeš, Julius, Volf, Petr, Votýpka, Jan, Yurchenko, Vyacheslav
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969907/
https://www.ncbi.nlm.nih.gov/pubmed/31744234
http://dx.doi.org/10.3390/pathogens8040241
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author Kraeva, Natalya
Leštinová, Tereza
Ishemgulova, Aygul
Majerová, Karolina
Butenko, Anzhelika
Vaselek, Slavica
Bespyatykh, Julia
Charyyeva, Arzuv
Spitzová, Tatiana
Kostygov, Alexei Yu.
Lukeš, Julius
Volf, Petr
Votýpka, Jan
Yurchenko, Vyacheslav
author_facet Kraeva, Natalya
Leštinová, Tereza
Ishemgulova, Aygul
Majerová, Karolina
Butenko, Anzhelika
Vaselek, Slavica
Bespyatykh, Julia
Charyyeva, Arzuv
Spitzová, Tatiana
Kostygov, Alexei Yu.
Lukeš, Julius
Volf, Petr
Votýpka, Jan
Yurchenko, Vyacheslav
author_sort Kraeva, Natalya
collection PubMed
description Protein phosphorylation/dephosphorylation is an important regulatory mechanism that controls many key physiological processes. Numerous pathogens successfully use kinases and phosphatases to internalize, replicate, and survive, modifying the host′s phosphorylation profile or signal transduction pathways. Multiple phosphatases and kinases from diverse bacterial pathogens have been implicated in human infections before. In this work, we have identified and characterized the dual specificity protein/lipid phosphatase LmDUSP1 as a novel virulence factor governing Leishmania mexicana infection. The LmDUSP1-encoding gene (LmxM.22.0250 in L. mexicana) has been acquired from bacteria via horizontal gene transfer. Importantly, its orthologues have been associated with virulence in several bacterial species, such as Mycobacterium tuberculosis and Listeria monocytogenes. Leishmania mexicana with ablated LmxM.22.0250 demonstrated severely attenuated virulence in the experimental infection of primary mouse macrophages, suggesting that this gene facilitates Leishmania pathogenicity in vertebrates. Despite significant upregulation of LmxM.22.0250 expression in metacyclic promastigotes, its ablation did not affect the ability of mutant cells to differentiate into virulent stages in insects. It remains to be further investigated which specific biochemical pathways involve LmDUSP1 and how this facilitates the parasite′s survival in the host. One of the interesting possibilities is that LmDUSP1 may target host′s substrate(s), thereby affecting its signal transduction pathways.
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spelling pubmed-69699072020-02-04 LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro Kraeva, Natalya Leštinová, Tereza Ishemgulova, Aygul Majerová, Karolina Butenko, Anzhelika Vaselek, Slavica Bespyatykh, Julia Charyyeva, Arzuv Spitzová, Tatiana Kostygov, Alexei Yu. Lukeš, Julius Volf, Petr Votýpka, Jan Yurchenko, Vyacheslav Pathogens Article Protein phosphorylation/dephosphorylation is an important regulatory mechanism that controls many key physiological processes. Numerous pathogens successfully use kinases and phosphatases to internalize, replicate, and survive, modifying the host′s phosphorylation profile or signal transduction pathways. Multiple phosphatases and kinases from diverse bacterial pathogens have been implicated in human infections before. In this work, we have identified and characterized the dual specificity protein/lipid phosphatase LmDUSP1 as a novel virulence factor governing Leishmania mexicana infection. The LmDUSP1-encoding gene (LmxM.22.0250 in L. mexicana) has been acquired from bacteria via horizontal gene transfer. Importantly, its orthologues have been associated with virulence in several bacterial species, such as Mycobacterium tuberculosis and Listeria monocytogenes. Leishmania mexicana with ablated LmxM.22.0250 demonstrated severely attenuated virulence in the experimental infection of primary mouse macrophages, suggesting that this gene facilitates Leishmania pathogenicity in vertebrates. Despite significant upregulation of LmxM.22.0250 expression in metacyclic promastigotes, its ablation did not affect the ability of mutant cells to differentiate into virulent stages in insects. It remains to be further investigated which specific biochemical pathways involve LmDUSP1 and how this facilitates the parasite′s survival in the host. One of the interesting possibilities is that LmDUSP1 may target host′s substrate(s), thereby affecting its signal transduction pathways. MDPI 2019-11-17 /pmc/articles/PMC6969907/ /pubmed/31744234 http://dx.doi.org/10.3390/pathogens8040241 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kraeva, Natalya
Leštinová, Tereza
Ishemgulova, Aygul
Majerová, Karolina
Butenko, Anzhelika
Vaselek, Slavica
Bespyatykh, Julia
Charyyeva, Arzuv
Spitzová, Tatiana
Kostygov, Alexei Yu.
Lukeš, Julius
Volf, Petr
Votýpka, Jan
Yurchenko, Vyacheslav
LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro
title LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro
title_full LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro
title_fullStr LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro
title_full_unstemmed LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro
title_short LmxM.22.0250-Encoded Dual Specificity Protein/Lipid Phosphatase Impairs Leishmania mexicana Virulence In Vitro
title_sort lmxm.22.0250-encoded dual specificity protein/lipid phosphatase impairs leishmania mexicana virulence in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969907/
https://www.ncbi.nlm.nih.gov/pubmed/31744234
http://dx.doi.org/10.3390/pathogens8040241
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