Cargando…

Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)

Lymphatic filariasis (LF) threatens nearly 20% of the world’s population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the m...

Descripción completa

Detalles Bibliográficos
Autores principales: Maclean, Mary J., Lorenz, W. Walter, Dzimianski, Michael T., Anna, Christopher, Moorhead, Andrew R., Reaves, Barbara J., Wolstenholme, Adrian J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994942/
https://www.ncbi.nlm.nih.gov/pubmed/33777408
http://dx.doi.org/10.1017/pao.2019.1
_version_ 1783669861780553728
author Maclean, Mary J.
Lorenz, W. Walter
Dzimianski, Michael T.
Anna, Christopher
Moorhead, Andrew R.
Reaves, Barbara J.
Wolstenholme, Adrian J.
author_facet Maclean, Mary J.
Lorenz, W. Walter
Dzimianski, Michael T.
Anna, Christopher
Moorhead, Andrew R.
Reaves, Barbara J.
Wolstenholme, Adrian J.
author_sort Maclean, Mary J.
collection PubMed
description Lymphatic filariasis (LF) threatens nearly 20% of the world’s population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood. To gain a better insight into antifilarial drug action in vivo, we treated gerbils harbouring patent Brugia malayi infections with 6 mg kg(−1) DEC, 0.15 mg kg(−1) ivermectin or 1 mg kg(−1) albendazole. Treatments had no effect on the numbers of worms present in the peritoneal cavity of treated animals, so effects on gene expression were a direct result of the drug and not complicated by dying parasites. Adults and microfilariae were collected 1 and 7 days post-treatment and RNA isolated for transcriptomic analysis. The experiment was repeated three times. Ivermectin treatment produced the most differentially expressed genes (DEGs), 113. DEC treatment yielded 61 DEGs. Albendazole treatment resulted in little change in gene expression, with only 6 genes affected. In total, nearly 200 DEGs were identified with little overlap between treatment groups, suggesting that these drugs may interfere in different ways with processes important for parasite survival, development, and reproduction.
format Online
Article
Text
id pubmed-7994942
institution National Center for Biotechnology Information
language English
publishDate 2019
record_format MEDLINE/PubMed
spelling pubmed-79949422021-03-26 Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus) Maclean, Mary J. Lorenz, W. Walter Dzimianski, Michael T. Anna, Christopher Moorhead, Andrew R. Reaves, Barbara J. Wolstenholme, Adrian J. Parasitol Open Article Lymphatic filariasis (LF) threatens nearly 20% of the world’s population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood. To gain a better insight into antifilarial drug action in vivo, we treated gerbils harbouring patent Brugia malayi infections with 6 mg kg(−1) DEC, 0.15 mg kg(−1) ivermectin or 1 mg kg(−1) albendazole. Treatments had no effect on the numbers of worms present in the peritoneal cavity of treated animals, so effects on gene expression were a direct result of the drug and not complicated by dying parasites. Adults and microfilariae were collected 1 and 7 days post-treatment and RNA isolated for transcriptomic analysis. The experiment was repeated three times. Ivermectin treatment produced the most differentially expressed genes (DEGs), 113. DEC treatment yielded 61 DEGs. Albendazole treatment resulted in little change in gene expression, with only 6 genes affected. In total, nearly 200 DEGs were identified with little overlap between treatment groups, suggesting that these drugs may interfere in different ways with processes important for parasite survival, development, and reproduction. 2019-03-08 2019 /pmc/articles/PMC7994942/ /pubmed/33777408 http://dx.doi.org/10.1017/pao.2019.1 Text en This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Maclean, Mary J.
Lorenz, W. Walter
Dzimianski, Michael T.
Anna, Christopher
Moorhead, Andrew R.
Reaves, Barbara J.
Wolstenholme, Adrian J.
Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)
title Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)
title_full Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)
title_fullStr Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)
title_full_unstemmed Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)
title_short Effects of diethylcarbamazine and ivermectin treatment on Brugia malayi gene expression in infected gerbils (Meriones unguiculatus)
title_sort effects of diethylcarbamazine and ivermectin treatment on brugia malayi gene expression in infected gerbils (meriones unguiculatus)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994942/
https://www.ncbi.nlm.nih.gov/pubmed/33777408
http://dx.doi.org/10.1017/pao.2019.1
work_keys_str_mv AT macleanmaryj effectsofdiethylcarbamazineandivermectintreatmentonbrugiamalayigeneexpressionininfectedgerbilsmerionesunguiculatus
AT lorenzwwalter effectsofdiethylcarbamazineandivermectintreatmentonbrugiamalayigeneexpressionininfectedgerbilsmerionesunguiculatus
AT dzimianskimichaelt effectsofdiethylcarbamazineandivermectintreatmentonbrugiamalayigeneexpressionininfectedgerbilsmerionesunguiculatus
AT annachristopher effectsofdiethylcarbamazineandivermectintreatmentonbrugiamalayigeneexpressionininfectedgerbilsmerionesunguiculatus
AT moorheadandrewr effectsofdiethylcarbamazineandivermectintreatmentonbrugiamalayigeneexpressionininfectedgerbilsmerionesunguiculatus
AT reavesbarbaraj effectsofdiethylcarbamazineandivermectintreatmentonbrugiamalayigeneexpressionininfectedgerbilsmerionesunguiculatus
AT wolstenholmeadrianj effectsofdiethylcarbamazineandivermectintreatmentonbrugiamalayigeneexpressionininfectedgerbilsmerionesunguiculatus