Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance.

<h4>Background</h4>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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/86f669650eef4fdf80d0e28f19248226
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:86f669650eef4fdf80d0e28f19248226
record_format	dspace
spelling	oai:doaj.org-article:86f669650eef4fdf80d0e28f192482262021-12-02T20:24:02ZCharacterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance.1935-27271935-273510.1371/journal.pntd.0009777https://doaj.org/article/86f669650eef4fdf80d0e28f192482262021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009777https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>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.<h4>Methodology and principal findings</h4>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.<h4>Significance</h4>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.Sara RooseRussell W AvramenkoStephen M J PolloJames D WasmuthShaali AmeMio AyanaMartha BetsonPiet CoolsDaniel DanaBen P JonesZeleke MekonnenArianna MorosettiAbhinaya VenkatesanJohnny VlaminckMatthew L WorkentineBruno LeveckeJohn S GilleardPeter GeldhofPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009777 (2021)
institution	DOAJ
collection	DOAJ
language	EN
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.
description	<h4>Background</h4>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.<h4>Methodology and principal findings</h4>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.<h4>Significance</h4>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
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://doaj.org/article/86f669650eef4fdf80d0e28f19248226
work_keys_str_mv	AT sararoose characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT russellwavramenko characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT stephenmjpollo characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT jamesdwasmuth characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT shaaliame characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT mioayana characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT marthabetson characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT pietcools characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT danieldana characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT benpjones characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT zelekemekonnen characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT ariannamorosetti characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT abhinayavenkatesan characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT johnnyvlaminck characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT matthewlworkentine characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT brunolevecke characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT johnsgilleard characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance AT petergeldhof characterizationofthebtubulingenefamilyinascarislumbricoidesandascarissuumanditsimplicationforthemoleculardetectionofbenzimidazoleresistance
_version_	1718374060204752896

Characterization of the β-tubulin gene family in Ascaris lumbricoides and Ascaris suum and its implication for the molecular detection of benzimidazole resistance.

Ejemplares similares