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Essential role of a Plasmodium berghei heat shock protein (PBANKA_0938300) in gametocyte development

The continued existence of Plasmodium parasites in physiologically distinct environments during their transmission in mosquitoes and vertebrate hosts requires effector proteins encoded by parasite genes to provide adaptability. Parasites utilize their robust stress response system involving heat sho...

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Detalles Bibliográficos
Autores principales: Kashif, Mohammad, Quadiri, Afshana, Singh, Agam Prasad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654831/
https://www.ncbi.nlm.nih.gov/pubmed/34880324
http://dx.doi.org/10.1038/s41598-021-03059-4
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author Kashif, Mohammad
Quadiri, Afshana
Singh, Agam Prasad
author_facet Kashif, Mohammad
Quadiri, Afshana
Singh, Agam Prasad
author_sort Kashif, Mohammad
collection PubMed
description The continued existence of Plasmodium parasites in physiologically distinct environments during their transmission in mosquitoes and vertebrate hosts requires effector proteins encoded by parasite genes to provide adaptability. Parasites utilize their robust stress response system involving heat shock proteins for their survival. Molecular chaperones are involved in maintaining protein homeostasis within a cell during stress, protein biogenesis and the formation of protein complexes. Due to their critical role in parasite virulence, they are considered targets for therapeutic interventions. Our results identified a putative P. berghei heat shock protein (HSP) belonging to the HSP40 family (HspJ62), which is abundantly induced upon heat stress and expressed during all parasite stages. To determine the role HspJ62, a gene-disrupted P. berghei transgenic line was developed (ΔHspJ62), which resulted in disruption of gametocyte formation. Such parasites were unable to form subsequent sexual stages because of disrupted gametogenesis, indicating the essential role of HspJ62 in gametocyte formation. Transcriptomic analysis of the transgenic line showed downregulation of a number of genes, most of which were specific to male or female gametocytes. The transcription factor ApiAP2 was also downregulated in ΔHspJ62 parasites. Our findings suggest that the downregulation of ApiAP2 likely disrupts the transcriptional regulation of sexual stage genes, leading to impaired gametogenesis. This finding also highlights the critical role that HspJ62 indirectly plays in the development of P. berghei sexual stages and in facilitating the conversion from the asexual blood stage to the sexual stage. This study characterizes the HspJ62 protein as a fertility factor because parasites lacking it are unable to transmit to mosquitoes. This study adds an important contribution to ongoing research aimed at understanding gametocyte differentiation and formation in parasites. The molecule adds to the list of potential drug targets that can be targeted to inhibit parasite sexual development and consequently parasite transmission.
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spelling pubmed-86548312021-12-09 Essential role of a Plasmodium berghei heat shock protein (PBANKA_0938300) in gametocyte development Kashif, Mohammad Quadiri, Afshana Singh, Agam Prasad Sci Rep Article The continued existence of Plasmodium parasites in physiologically distinct environments during their transmission in mosquitoes and vertebrate hosts requires effector proteins encoded by parasite genes to provide adaptability. Parasites utilize their robust stress response system involving heat shock proteins for their survival. Molecular chaperones are involved in maintaining protein homeostasis within a cell during stress, protein biogenesis and the formation of protein complexes. Due to their critical role in parasite virulence, they are considered targets for therapeutic interventions. Our results identified a putative P. berghei heat shock protein (HSP) belonging to the HSP40 family (HspJ62), which is abundantly induced upon heat stress and expressed during all parasite stages. To determine the role HspJ62, a gene-disrupted P. berghei transgenic line was developed (ΔHspJ62), which resulted in disruption of gametocyte formation. Such parasites were unable to form subsequent sexual stages because of disrupted gametogenesis, indicating the essential role of HspJ62 in gametocyte formation. Transcriptomic analysis of the transgenic line showed downregulation of a number of genes, most of which were specific to male or female gametocytes. The transcription factor ApiAP2 was also downregulated in ΔHspJ62 parasites. Our findings suggest that the downregulation of ApiAP2 likely disrupts the transcriptional regulation of sexual stage genes, leading to impaired gametogenesis. This finding also highlights the critical role that HspJ62 indirectly plays in the development of P. berghei sexual stages and in facilitating the conversion from the asexual blood stage to the sexual stage. This study characterizes the HspJ62 protein as a fertility factor because parasites lacking it are unable to transmit to mosquitoes. This study adds an important contribution to ongoing research aimed at understanding gametocyte differentiation and formation in parasites. The molecule adds to the list of potential drug targets that can be targeted to inhibit parasite sexual development and consequently parasite transmission. Nature Publishing Group UK 2021-12-08 /pmc/articles/PMC8654831/ /pubmed/34880324 http://dx.doi.org/10.1038/s41598-021-03059-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kashif, Mohammad
Quadiri, Afshana
Singh, Agam Prasad
Essential role of a Plasmodium berghei heat shock protein (PBANKA_0938300) in gametocyte development
title Essential role of a Plasmodium berghei heat shock protein (PBANKA_0938300) in gametocyte development
title_full Essential role of a Plasmodium berghei heat shock protein (PBANKA_0938300) in gametocyte development
title_fullStr Essential role of a Plasmodium berghei heat shock protein (PBANKA_0938300) in gametocyte development
title_full_unstemmed Essential role of a Plasmodium berghei heat shock protein (PBANKA_0938300) in gametocyte development
title_short Essential role of a Plasmodium berghei heat shock protein (PBANKA_0938300) in gametocyte development
title_sort essential role of a plasmodium berghei heat shock protein (pbanka_0938300) in gametocyte development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654831/
https://www.ncbi.nlm.nih.gov/pubmed/34880324
http://dx.doi.org/10.1038/s41598-021-03059-4
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