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How Malaria Parasites Acquire Nutrients From Their Host
Plasmodium parasites responsible for the disease malaria reside within erythrocytes. Inside this niche host cell, parasites internalize and digest host hemoglobin to source amino acids required for protein production. However, hemoglobin does not contain isoleucine, an amino acid essential for Plasm...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027349/ https://www.ncbi.nlm.nih.gov/pubmed/33842474 http://dx.doi.org/10.3389/fcell.2021.649184 |
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author | Counihan, Natalie A. Modak, Joyanta K. de Koning-Ward, Tania F. |
author_facet | Counihan, Natalie A. Modak, Joyanta K. de Koning-Ward, Tania F. |
author_sort | Counihan, Natalie A. |
collection | PubMed |
description | Plasmodium parasites responsible for the disease malaria reside within erythrocytes. Inside this niche host cell, parasites internalize and digest host hemoglobin to source amino acids required for protein production. However, hemoglobin does not contain isoleucine, an amino acid essential for Plasmodium growth, and the parasite cannot synthesize it de novo. The parasite is also more metabolically active than its host cell, and the rate at which some nutrients are consumed exceeds the rate at which they can be taken up by erythrocyte transporters. To overcome these constraints, Plasmodium parasites increase the permeability of the erythrocyte membrane to isoleucine and other low-molecular-weight solutes it requires for growth by forming new permeation pathways (NPPs). In addition to the erythrocyte membrane, host nutrients also need to cross the encasing parasitophorous vacuole membrane (PVM) and the parasite plasma membrane to access the parasite. This review outlines recent advances that have been made in identifying the molecular constituents of the NPPs, the PVM nutrient channel, and the endocytic apparatus that transports host hemoglobin and identifies key knowledge gaps that remain. Importantly, blocking the ability of Plasmodium to source essential nutrients is lethal to the parasite, and thus, components of these key pathways represent potential antimalaria drug targets. |
format | Online Article Text |
id | pubmed-8027349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80273492021-04-09 How Malaria Parasites Acquire Nutrients From Their Host Counihan, Natalie A. Modak, Joyanta K. de Koning-Ward, Tania F. Front Cell Dev Biol Cell and Developmental Biology Plasmodium parasites responsible for the disease malaria reside within erythrocytes. Inside this niche host cell, parasites internalize and digest host hemoglobin to source amino acids required for protein production. However, hemoglobin does not contain isoleucine, an amino acid essential for Plasmodium growth, and the parasite cannot synthesize it de novo. The parasite is also more metabolically active than its host cell, and the rate at which some nutrients are consumed exceeds the rate at which they can be taken up by erythrocyte transporters. To overcome these constraints, Plasmodium parasites increase the permeability of the erythrocyte membrane to isoleucine and other low-molecular-weight solutes it requires for growth by forming new permeation pathways (NPPs). In addition to the erythrocyte membrane, host nutrients also need to cross the encasing parasitophorous vacuole membrane (PVM) and the parasite plasma membrane to access the parasite. This review outlines recent advances that have been made in identifying the molecular constituents of the NPPs, the PVM nutrient channel, and the endocytic apparatus that transports host hemoglobin and identifies key knowledge gaps that remain. Importantly, blocking the ability of Plasmodium to source essential nutrients is lethal to the parasite, and thus, components of these key pathways represent potential antimalaria drug targets. Frontiers Media S.A. 2021-03-25 /pmc/articles/PMC8027349/ /pubmed/33842474 http://dx.doi.org/10.3389/fcell.2021.649184 Text en Copyright © 2021 Counihan, Modak and de Koning-Ward. https://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 | Cell and Developmental Biology Counihan, Natalie A. Modak, Joyanta K. de Koning-Ward, Tania F. How Malaria Parasites Acquire Nutrients From Their Host |
title | How Malaria Parasites Acquire Nutrients From Their Host |
title_full | How Malaria Parasites Acquire Nutrients From Their Host |
title_fullStr | How Malaria Parasites Acquire Nutrients From Their Host |
title_full_unstemmed | How Malaria Parasites Acquire Nutrients From Their Host |
title_short | How Malaria Parasites Acquire Nutrients From Their Host |
title_sort | how malaria parasites acquire nutrients from their host |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027349/ https://www.ncbi.nlm.nih.gov/pubmed/33842474 http://dx.doi.org/10.3389/fcell.2021.649184 |
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