Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance.
Background The treatment coverage of control programs providing benzimidazole (BZ) drugs to eliminate the morbidity caused by soil-transmitted helminths (STHs) is unprecedently high. This high drug pressure may result in the development of BZ resistance in STHs and so there is an urgent need for sur...
Published in: | PLOS Neglected Tropical Diseases |
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2021
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Online Access: | https://doi.org/10.1371/journal.pntd.0009777 https://doaj.org/article/86f669650eef4fdf80d0e28f19248226 |
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ftdoajarticles:oai:doaj.org/article:86f669650eef4fdf80d0e28f19248226 2023-05-15T15:18:33+02:00 Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance. Sara Roose Russell W Avramenko Stephen M J Pollo James D Wasmuth Shaali Ame Mio Ayana Martha Betson Piet Cools Daniel Dana Ben P Jones Zeleke Mekonnen Arianna Morosetti Abhinaya Venkatesan Johnny Vlaminck Matthew L Workentine Bruno Levecke John S Gilleard Peter Geldhof 2021-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009777 https://doaj.org/article/86f669650eef4fdf80d0e28f19248226 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009777 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009777 https://doaj.org/article/86f669650eef4fdf80d0e28f19248226 PLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009777 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009777 2022-12-31T11:29:28Z Background The treatment coverage of control programs providing benzimidazole (BZ) drugs to eliminate the morbidity caused by soil-transmitted helminths (STHs) is unprecedently high. This high drug pressure may result in the development of BZ resistance in STHs and so there is an urgent need for surveillance systems detecting molecular markers associated with BZ resistance. A critical prerequisite to develop such systems is an understanding of the gene family encoding β-tubulin proteins, the principal targets of BZ drugs. Methodology and principal findings First, the β-tubulin gene families of Ascaris lumbricoides and Ascaris suum were characterized through the analysis of published genomes. Second, RNA-seq and RT-PCR analyses on cDNA were applied to determine the transcription profiles of the different gene family members. The results revealed that Ascaris species have at least seven different β-tubulin genes of which two are highly expressed during the entire lifecycle. Third, deep amplicon sequencing was performed on these two genes in more than 200 adult A. lumbricoides (Ethiopia and Tanzania) and A. suum (Belgium) worms, to investigate the intra- and inter-species genetic diversity and the presence of single nucleotide polymorphisms (SNPs) that are associated with BZ resistance in other helminth species; F167Y (TTC>TAC or TTT>TAT), E198A (GAA>GCA or GAG>GCG), E198L (GAA>TTA) and F200Y (TTC>TAC or TTT>TAT). These particular SNPs were absent in the two investigated genes in all three Ascaris populations. Significance This study demonstrated the presence of at least seven β-tubulin genes in Ascaris worms. A new nomenclature was proposed and prioritization of genes for future BZ resistance research was discussed. This is the first comprehensive description of the β-tubulin gene family in Ascaris and provides a framework to investigate the prevalence and potential role of β-tubulin sequence polymorphisms in BZ resistance in a more systematic manner than previously possible. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Tac ENVELOPE(-59.517,-59.517,-62.500,-62.500) PLOS Neglected Tropical Diseases 15 9 e0009777 |
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 Sara Roose Russell W Avramenko Stephen M J Pollo James D Wasmuth Shaali Ame Mio Ayana Martha Betson Piet Cools Daniel Dana Ben P Jones Zeleke Mekonnen Arianna Morosetti Abhinaya Venkatesan Johnny Vlaminck Matthew L Workentine Bruno Levecke John S Gilleard Peter Geldhof Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Background The treatment coverage of control programs providing benzimidazole (BZ) drugs to eliminate the morbidity caused by soil-transmitted helminths (STHs) is unprecedently high. This high drug pressure may result in the development of BZ resistance in STHs and so there is an urgent need for surveillance systems detecting molecular markers associated with BZ resistance. A critical prerequisite to develop such systems is an understanding of the gene family encoding β-tubulin proteins, the principal targets of BZ drugs. Methodology and principal findings First, the β-tubulin gene families of Ascaris lumbricoides and Ascaris suum were characterized through the analysis of published genomes. Second, RNA-seq and RT-PCR analyses on cDNA were applied to determine the transcription profiles of the different gene family members. The results revealed that Ascaris species have at least seven different β-tubulin genes of which two are highly expressed during the entire lifecycle. Third, deep amplicon sequencing was performed on these two genes in more than 200 adult A. lumbricoides (Ethiopia and Tanzania) and A. suum (Belgium) worms, to investigate the intra- and inter-species genetic diversity and the presence of single nucleotide polymorphisms (SNPs) that are associated with BZ resistance in other helminth species; F167Y (TTC>TAC or TTT>TAT), E198A (GAA>GCA or GAG>GCG), E198L (GAA>TTA) and F200Y (TTC>TAC or TTT>TAT). These particular SNPs were absent in the two investigated genes in all three Ascaris populations. Significance This study demonstrated the presence of at least seven β-tubulin genes in Ascaris worms. A new nomenclature was proposed and prioritization of genes for future BZ resistance research was discussed. This is the first comprehensive description of the β-tubulin gene family in Ascaris and provides a framework to investigate the prevalence and potential role of β-tubulin sequence polymorphisms in BZ resistance in a more systematic manner than previously possible. |
format |
Article in Journal/Newspaper |
author |
Sara Roose Russell W Avramenko Stephen M J Pollo James D Wasmuth Shaali Ame Mio Ayana Martha Betson Piet Cools Daniel Dana Ben P Jones Zeleke Mekonnen Arianna Morosetti Abhinaya Venkatesan Johnny Vlaminck Matthew L Workentine Bruno Levecke John S Gilleard Peter Geldhof |
author_facet |
Sara Roose Russell W Avramenko Stephen M J Pollo James D Wasmuth Shaali Ame Mio Ayana Martha Betson Piet Cools Daniel Dana Ben P Jones Zeleke Mekonnen Arianna Morosetti Abhinaya Venkatesan Johnny Vlaminck Matthew L Workentine Bruno Levecke John S Gilleard Peter Geldhof |
author_sort |
Sara Roose |
title |
Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance. |
title_short |
Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance. |
title_full |
Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance. |
title_fullStr |
Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance. |
title_full_unstemmed |
Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance. |
title_sort |
characterization of the β-tubulin gene family in ascaris lumbricoides and ascaris suum and its implication for the molecular detection of benzimidazole resistance. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0009777 https://doaj.org/article/86f669650eef4fdf80d0e28f19248226 |
long_lat |
ENVELOPE(-59.517,-59.517,-62.500,-62.500) |
geographic |
Arctic Tac |
geographic_facet |
Arctic Tac |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009777 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009777 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009777 https://doaj.org/article/86f669650eef4fdf80d0e28f19248226 |
op_doi |
https://doi.org/10.1371/journal.pntd.0009777 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
9 |
container_start_page |
e0009777 |
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