Cargando…
Newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles
Infections by parasitic nematodes cause large health and economic burdens worldwide. We use anthelmintic drugs to reduce these infections. However, resistance to anthelmintic drugs is extremely common and increasing worldwide. It is essential to understand the mechanisms of resistance to slow its sp...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503852/ https://www.ncbi.nlm.nih.gov/pubmed/34637983 http://dx.doi.org/10.1016/j.ijpddr.2021.09.006 |
_version_ | 1784581211894579200 |
---|---|
author | Dilks, Clayton M. Koury, Emily J. Buchanan, Claire M. Andersen, Erik C. |
author_facet | Dilks, Clayton M. Koury, Emily J. Buchanan, Claire M. Andersen, Erik C. |
author_sort | Dilks, Clayton M. |
collection | PubMed |
description | Infections by parasitic nematodes cause large health and economic burdens worldwide. We use anthelmintic drugs to reduce these infections. However, resistance to anthelmintic drugs is extremely common and increasing worldwide. It is essential to understand the mechanisms of resistance to slow its spread. Recently, four new parasitic nematode beta-tubulin alleles have been identified in benzimidazole (BZ) resistant parasite populations: E198I, E198K, E198T, and E198stop. These alleles have not been tested for the ability to confer resistance or for any effects that they might have on organismal fitness. We introduced these four new alleles into the sensitive C. elegans laboratory-adapted N2 strain and exposed these genome-edited strains to both albendazole and fenbendazole. We found that all four alleles conferred resistance to both BZ drugs. Additionally, we tested for fitness consequences in both control and albendazole conditions over seven generations in competitive fitness assays. We found that none of the edited alleles had deleterious effects on fitness in control conditions and that all four alleles conferred strong and equivalent fitness benefits in BZ drug conditions. Because it is unknown if previously validated alleles confer a dominant or recessive BZ resistance phenotype, we tested the phenotypes caused by five of these alleles and found that none of them conferred a dominant BZ resistance phenotype. Accurate measurements of resistance, fitness effects, and dominance caused by the resistance alleles allow for the generation of better models of population dynamics and facilitate control practices that maximize the efficacy of this critical anthelmintic drug class. |
format | Online Article Text |
id | pubmed-8503852 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-85038522021-10-15 Newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles Dilks, Clayton M. Koury, Emily J. Buchanan, Claire M. Andersen, Erik C. Int J Parasitol Drugs Drug Resist Regular article Infections by parasitic nematodes cause large health and economic burdens worldwide. We use anthelmintic drugs to reduce these infections. However, resistance to anthelmintic drugs is extremely common and increasing worldwide. It is essential to understand the mechanisms of resistance to slow its spread. Recently, four new parasitic nematode beta-tubulin alleles have been identified in benzimidazole (BZ) resistant parasite populations: E198I, E198K, E198T, and E198stop. These alleles have not been tested for the ability to confer resistance or for any effects that they might have on organismal fitness. We introduced these four new alleles into the sensitive C. elegans laboratory-adapted N2 strain and exposed these genome-edited strains to both albendazole and fenbendazole. We found that all four alleles conferred resistance to both BZ drugs. Additionally, we tested for fitness consequences in both control and albendazole conditions over seven generations in competitive fitness assays. We found that none of the edited alleles had deleterious effects on fitness in control conditions and that all four alleles conferred strong and equivalent fitness benefits in BZ drug conditions. Because it is unknown if previously validated alleles confer a dominant or recessive BZ resistance phenotype, we tested the phenotypes caused by five of these alleles and found that none of them conferred a dominant BZ resistance phenotype. Accurate measurements of resistance, fitness effects, and dominance caused by the resistance alleles allow for the generation of better models of population dynamics and facilitate control practices that maximize the efficacy of this critical anthelmintic drug class. Elsevier 2021-10-08 /pmc/articles/PMC8503852/ /pubmed/34637983 http://dx.doi.org/10.1016/j.ijpddr.2021.09.006 Text en © 2021 Published by Elsevier Ltd on behalf of Australian Society for Parasitology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Regular article Dilks, Clayton M. Koury, Emily J. Buchanan, Claire M. Andersen, Erik C. Newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles |
title | Newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles |
title_full | Newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles |
title_fullStr | Newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles |
title_full_unstemmed | Newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles |
title_short | Newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles |
title_sort | newly identified parasitic nematode beta-tubulin alleles confer resistance to benzimidazoles |
topic | Regular article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503852/ https://www.ncbi.nlm.nih.gov/pubmed/34637983 http://dx.doi.org/10.1016/j.ijpddr.2021.09.006 |
work_keys_str_mv | AT dilksclaytonm newlyidentifiedparasiticnematodebetatubulinallelesconferresistancetobenzimidazoles AT kouryemilyj newlyidentifiedparasiticnematodebetatubulinallelesconferresistancetobenzimidazoles AT buchananclairem newlyidentifiedparasiticnematodebetatubulinallelesconferresistancetobenzimidazoles AT andersenerikc newlyidentifiedparasiticnematodebetatubulinallelesconferresistancetobenzimidazoles |