Cargando…

Vitamin B6 Acquisition and Metabolism in Schistosoma mansoni

Schistosomes are parasitic platyhelminths that currently infect >200 million people globally. The adult worms can live within the vasculature of their hosts for many years where they acquire all nutrients necessary for their survival and growth. In this work we focus on how Schistosoma mansoni pa...

Descripción completa

Detalles Bibliográficos
Autores principales: Da’dara, Akram A., Elzoheiry, Manal, El-Beshbishi, Samar N., Skelly, Patrick J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891054/
https://www.ncbi.nlm.nih.gov/pubmed/33613557
http://dx.doi.org/10.3389/fimmu.2020.622162
_version_ 1783652624406413312
author Da’dara, Akram A.
Elzoheiry, Manal
El-Beshbishi, Samar N.
Skelly, Patrick J.
author_facet Da’dara, Akram A.
Elzoheiry, Manal
El-Beshbishi, Samar N.
Skelly, Patrick J.
author_sort Da’dara, Akram A.
collection PubMed
description Schistosomes are parasitic platyhelminths that currently infect >200 million people globally. The adult worms can live within the vasculature of their hosts for many years where they acquire all nutrients necessary for their survival and growth. In this work we focus on how Schistosoma mansoni parasites acquire and metabolize vitamin B6, whose active form is pyridoxal phosphate (PLP). We show here that live intravascular stage parasites (schistosomula and adult males and females) can cleave exogenous PLP to liberate pyridoxal. Of the three characterized nucleotide-metabolizing ectoenzymes expressed at the schistosome surface (SmAP, SmNPP5, and SmATPDase1), only SmAP hydrolyzes PLP. Heat-inactivated recombinant SmAP can no longer cleave PLP. Further, parasites whose SmAP gene has been suppressed by RNAi are significantly impaired in their ability to cleave PLP compared to controls. When schistosomes are incubated in murine plasma, they alter its metabolomic profile—the levels of both pyridoxal and phosphate increase over time, a finding consistent with the action of host-exposed SmAP acting on PLP. We hypothesize that SmAP-mediated dephosphorylation of PLP generates a pool of pyridoxal around the worms that can be conveniently taken in by the parasites to participate in essential, vitamin B6-driven metabolism. In addition, since host PLP‐dependent enzymes play active roles in inflammatory processes, parasite-mediated cleavage of this metabolite may serve to limit parasite-damaging inflammation. In this work we also identified schistosome homologs of enzymes that are involved in intracellular vitamin B6 metabolism. These are pyridoxal kinase (SmPK) as well as pyridoxal phosphate phosphatase (SmPLP-Ph) and pyridox(am)ine 5’-phosphate oxidase (SmPNPO) and cDNAs encoding these three enzymes were cloned and sequenced. The three genes encoding these enzymes all display high relative expression in schistosomula and adult worms suggestive of robust vitamin B6 metabolism in the intravascular life stages.
format Online
Article
Text
id pubmed-7891054
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78910542021-02-19 Vitamin B6 Acquisition and Metabolism in Schistosoma mansoni Da’dara, Akram A. Elzoheiry, Manal El-Beshbishi, Samar N. Skelly, Patrick J. Front Immunol Immunology Schistosomes are parasitic platyhelminths that currently infect >200 million people globally. The adult worms can live within the vasculature of their hosts for many years where they acquire all nutrients necessary for their survival and growth. In this work we focus on how Schistosoma mansoni parasites acquire and metabolize vitamin B6, whose active form is pyridoxal phosphate (PLP). We show here that live intravascular stage parasites (schistosomula and adult males and females) can cleave exogenous PLP to liberate pyridoxal. Of the three characterized nucleotide-metabolizing ectoenzymes expressed at the schistosome surface (SmAP, SmNPP5, and SmATPDase1), only SmAP hydrolyzes PLP. Heat-inactivated recombinant SmAP can no longer cleave PLP. Further, parasites whose SmAP gene has been suppressed by RNAi are significantly impaired in their ability to cleave PLP compared to controls. When schistosomes are incubated in murine plasma, they alter its metabolomic profile—the levels of both pyridoxal and phosphate increase over time, a finding consistent with the action of host-exposed SmAP acting on PLP. We hypothesize that SmAP-mediated dephosphorylation of PLP generates a pool of pyridoxal around the worms that can be conveniently taken in by the parasites to participate in essential, vitamin B6-driven metabolism. In addition, since host PLP‐dependent enzymes play active roles in inflammatory processes, parasite-mediated cleavage of this metabolite may serve to limit parasite-damaging inflammation. In this work we also identified schistosome homologs of enzymes that are involved in intracellular vitamin B6 metabolism. These are pyridoxal kinase (SmPK) as well as pyridoxal phosphate phosphatase (SmPLP-Ph) and pyridox(am)ine 5’-phosphate oxidase (SmPNPO) and cDNAs encoding these three enzymes were cloned and sequenced. The three genes encoding these enzymes all display high relative expression in schistosomula and adult worms suggestive of robust vitamin B6 metabolism in the intravascular life stages. Frontiers Media S.A. 2021-02-04 /pmc/articles/PMC7891054/ /pubmed/33613557 http://dx.doi.org/10.3389/fimmu.2020.622162 Text en Copyright © 2021 Da’dara, Elzoheiry, El-Beshbishi and Skelly http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Da’dara, Akram A.
Elzoheiry, Manal
El-Beshbishi, Samar N.
Skelly, Patrick J.
Vitamin B6 Acquisition and Metabolism in Schistosoma mansoni
title Vitamin B6 Acquisition and Metabolism in Schistosoma mansoni
title_full Vitamin B6 Acquisition and Metabolism in Schistosoma mansoni
title_fullStr Vitamin B6 Acquisition and Metabolism in Schistosoma mansoni
title_full_unstemmed Vitamin B6 Acquisition and Metabolism in Schistosoma mansoni
title_short Vitamin B6 Acquisition and Metabolism in Schistosoma mansoni
title_sort vitamin b6 acquisition and metabolism in schistosoma mansoni
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891054/
https://www.ncbi.nlm.nih.gov/pubmed/33613557
http://dx.doi.org/10.3389/fimmu.2020.622162
work_keys_str_mv AT dadaraakrama vitaminb6acquisitionandmetabolisminschistosomamansoni
AT elzoheirymanal vitaminb6acquisitionandmetabolisminschistosomamansoni
AT elbeshbishisamarn vitaminb6acquisitionandmetabolisminschistosomamansoni
AT skellypatrickj vitaminb6acquisitionandmetabolisminschistosomamansoni