Impairing the maintenance of germinative cells in Echinococcus multilocularis by targeting Aurora kinase.
Background The tumor-like growth of the metacestode larvae of the tapeworm E. multilocularis causes human alveolar echinococcosis, a severe disease mainly affecting the liver. The germinative cells, a population of adult stem cells, are crucial for the larval growth and development of the parasite w...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2019
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0007425 https://doaj.org/article/9abaeea57c134bd0a3816f8cb91281fa |
id |
ftdoajarticles:oai:doaj.org/article:9abaeea57c134bd0a3816f8cb91281fa |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:9abaeea57c134bd0a3816f8cb91281fa 2023-05-15T15:13:13+02:00 Impairing the maintenance of germinative cells in Echinococcus multilocularis by targeting Aurora kinase. Zhe Cheng Fan Liu Huimin Tian Zhijian Xu Xiaoli Chai Damin Luo Yanhai Wang 2019-05-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007425 https://doaj.org/article/9abaeea57c134bd0a3816f8cb91281fa EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0007425 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007425 https://doaj.org/article/9abaeea57c134bd0a3816f8cb91281fa PLoS Neglected Tropical Diseases, Vol 13, Iss 5, p e0007425 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007425 2022-12-31T09:15:21Z Background The tumor-like growth of the metacestode larvae of the tapeworm E. multilocularis causes human alveolar echinococcosis, a severe disease mainly affecting the liver. The germinative cells, a population of adult stem cells, are crucial for the larval growth and development of the parasite within the hosts. Maintenance of the germinative cell pools relies on their abilities of extensive proliferation and self-renewal, which requires accurate control of the cell division cycle. Targeting regulators of the cell division progression may impair germinative cell populations, leading to impeded parasite growth. Methodology/principal findings In this study, we describe the characterization of EmAURKA and EmAURKB, which display significant similarity to the members of Aurora kinases that are essential mitotic kinases and play key roles in cell division. Our data suggest that EmAURKA and EmAURKB are actively expressed in the germinative cells of E. multilocularis. Treatment with low concentrations of MLN8237, a dual inhibitor of Aurora A and B, resulted in chromosomal defects in the germinative cells during mitosis, while higher concentrations of MLN8237 caused a failure in cytokinesis of the germinative cells, leading to multinucleated cells. Inhibition of the activities of Aurora kinases eventually resulted in depletion of the germinative cell populations in E. multilocularis, which in turn caused larval growth inhibition of the parasite. Conclusions/significance Our data demonstrate the vital roles of Aurora kinases in the regulation of mitotic progression and maintenance of the germinative cells in E. multilocularis, and suggest Aurora kinases as promising druggable targets for the development of novel chemotherapeutics against human alveolar echinococcosis. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 5 e0007425 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Zhe Cheng Fan Liu Huimin Tian Zhijian Xu Xiaoli Chai Damin Luo Yanhai Wang Impairing the maintenance of germinative cells in Echinococcus multilocularis by targeting Aurora kinase. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background The tumor-like growth of the metacestode larvae of the tapeworm E. multilocularis causes human alveolar echinococcosis, a severe disease mainly affecting the liver. The germinative cells, a population of adult stem cells, are crucial for the larval growth and development of the parasite within the hosts. Maintenance of the germinative cell pools relies on their abilities of extensive proliferation and self-renewal, which requires accurate control of the cell division cycle. Targeting regulators of the cell division progression may impair germinative cell populations, leading to impeded parasite growth. Methodology/principal findings In this study, we describe the characterization of EmAURKA and EmAURKB, which display significant similarity to the members of Aurora kinases that are essential mitotic kinases and play key roles in cell division. Our data suggest that EmAURKA and EmAURKB are actively expressed in the germinative cells of E. multilocularis. Treatment with low concentrations of MLN8237, a dual inhibitor of Aurora A and B, resulted in chromosomal defects in the germinative cells during mitosis, while higher concentrations of MLN8237 caused a failure in cytokinesis of the germinative cells, leading to multinucleated cells. Inhibition of the activities of Aurora kinases eventually resulted in depletion of the germinative cell populations in E. multilocularis, which in turn caused larval growth inhibition of the parasite. Conclusions/significance Our data demonstrate the vital roles of Aurora kinases in the regulation of mitotic progression and maintenance of the germinative cells in E. multilocularis, and suggest Aurora kinases as promising druggable targets for the development of novel chemotherapeutics against human alveolar echinococcosis. |
format |
Article in Journal/Newspaper |
author |
Zhe Cheng Fan Liu Huimin Tian Zhijian Xu Xiaoli Chai Damin Luo Yanhai Wang |
author_facet |
Zhe Cheng Fan Liu Huimin Tian Zhijian Xu Xiaoli Chai Damin Luo Yanhai Wang |
author_sort |
Zhe Cheng |
title |
Impairing the maintenance of germinative cells in Echinococcus multilocularis by targeting Aurora kinase. |
title_short |
Impairing the maintenance of germinative cells in Echinococcus multilocularis by targeting Aurora kinase. |
title_full |
Impairing the maintenance of germinative cells in Echinococcus multilocularis by targeting Aurora kinase. |
title_fullStr |
Impairing the maintenance of germinative cells in Echinococcus multilocularis by targeting Aurora kinase. |
title_full_unstemmed |
Impairing the maintenance of germinative cells in Echinococcus multilocularis by targeting Aurora kinase. |
title_sort |
impairing the maintenance of germinative cells in echinococcus multilocularis by targeting aurora kinase. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007425 https://doaj.org/article/9abaeea57c134bd0a3816f8cb91281fa |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 5, p e0007425 (2019) |
op_relation |
https://doi.org/10.1371/journal.pntd.0007425 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007425 https://doaj.org/article/9abaeea57c134bd0a3816f8cb91281fa |
op_doi |
https://doi.org/10.1371/journal.pntd.0007425 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
5 |
container_start_page |
e0007425 |
_version_ |
1766343795973029888 |