Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods

Abstract Multi-drug resistance is posing major challenges in suppressing the population of pests. Many herbivores develop resistance, causing a prolonged survival after exposure to a previously effective pesticide. Consequently, resistant pests reduce the yield of agricultural production, causing si...

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Autores principales:	Charbel Al Khoury, Nabil Nemer, Georges Nemer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/579e8042c47f4eb0a8d33dce81de52a4
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spelling	oai:doaj.org-article:579e8042c47f4eb0a8d33dce81de52a42021-12-02T16:53:18ZBeauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods10.1038/s41598-021-89622-52045-2322https://doaj.org/article/579e8042c47f4eb0a8d33dce81de52a42021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89622-5https://doaj.org/toc/2045-2322Abstract Multi-drug resistance is posing major challenges in suppressing the population of pests. Many herbivores develop resistance, causing a prolonged survival after exposure to a previously effective pesticide. Consequently, resistant pests reduce the yield of agricultural production, causing significant economic losses and reducing food security. Therefore, overpowering resistance acquisition of crop pests is a must. The ATP binding cassette transporters (ABC transporters) are considered as the main participants to the pesticide efflux and their neutralization will greatly contribute to potentiate failed treatments. Real-Time PCR analysis of 19 ABC transporter genes belonging to the ABCB, ABCC, ABCG, and ABCH revealed that a broad range of efflux pumps is activated in response to the exposure to pesticides. In this study, we used beauvericin (BEA), a known ABC transporters modulator, to resensitize different strains of Tetranychus urticae after artificial selection for resistance to cyflumetofen, bifenazate, and abamectin. Our results showed that the combinatorial treatment of pesticide (manufacturer’s recommended doses) + BEA (sublethal doses: 0.15 mg/L) significantly suppressed the resistant populations of T. urticae when compared to single-drug treatments. Moreover, after selective pressure for 40 generations, the LC50 values were significantly reduced from 36.5, 44.7, and 94.5 (pesticide) to 8.3, 12.5, and 23.4 (pesticide + BEA) for cyflumetofen, bifenazate, and abamectin, respectively. While the downstream targets for BEA are still elusive, we demonstrated hereby that it synergizes with sub-lethal doses of different pesticides and increases their effect by inhibiting ABC transporters. This is the first report to document such combinatorial activity of BEA against higher invertebrates paving the way for its usage in treating refractory cases of resistance to pesticides. Moreover, we demonstrated, for the first time, using in silico techniques, the higher affinity of BEA to ABC transformers subfamilies when compared to xenobiotics; thus, elucidating the pathway of the mycotoxin.Charbel Al KhouryNabil NemerGeorges NemerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Charbel Al Khoury Nabil Nemer Georges Nemer Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods
description	Abstract Multi-drug resistance is posing major challenges in suppressing the population of pests. Many herbivores develop resistance, causing a prolonged survival after exposure to a previously effective pesticide. Consequently, resistant pests reduce the yield of agricultural production, causing significant economic losses and reducing food security. Therefore, overpowering resistance acquisition of crop pests is a must. The ATP binding cassette transporters (ABC transporters) are considered as the main participants to the pesticide efflux and their neutralization will greatly contribute to potentiate failed treatments. Real-Time PCR analysis of 19 ABC transporter genes belonging to the ABCB, ABCC, ABCG, and ABCH revealed that a broad range of efflux pumps is activated in response to the exposure to pesticides. In this study, we used beauvericin (BEA), a known ABC transporters modulator, to resensitize different strains of Tetranychus urticae after artificial selection for resistance to cyflumetofen, bifenazate, and abamectin. Our results showed that the combinatorial treatment of pesticide (manufacturer’s recommended doses) + BEA (sublethal doses: 0.15 mg/L) significantly suppressed the resistant populations of T. urticae when compared to single-drug treatments. Moreover, after selective pressure for 40 generations, the LC50 values were significantly reduced from 36.5, 44.7, and 94.5 (pesticide) to 8.3, 12.5, and 23.4 (pesticide + BEA) for cyflumetofen, bifenazate, and abamectin, respectively. While the downstream targets for BEA are still elusive, we demonstrated hereby that it synergizes with sub-lethal doses of different pesticides and increases their effect by inhibiting ABC transporters. This is the first report to document such combinatorial activity of BEA against higher invertebrates paving the way for its usage in treating refractory cases of resistance to pesticides. Moreover, we demonstrated, for the first time, using in silico techniques, the higher affinity of BEA to ABC transformers subfamilies when compared to xenobiotics; thus, elucidating the pathway of the mycotoxin.
format	article
author	Charbel Al Khoury Nabil Nemer Georges Nemer
author_facet	Charbel Al Khoury Nabil Nemer Georges Nemer
author_sort	Charbel Al Khoury
title	Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods
title_short	Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods
title_full	Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods
title_fullStr	Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods
title_full_unstemmed	Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods
title_sort	beauvericin potentiates the activity of pesticides by neutralizing the atp-binding cassette transporters in arthropods
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/579e8042c47f4eb0a8d33dce81de52a4
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Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods

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