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Cytochrome P450 and Glutathione S-Transferase Confer Metabolic Resistance to SYP-14288 and Multi-Drug Resistance in Rhizoctonia solani

SYP-14288 is a fungicide as an uncoupler of oxidative phosphorylation, which is effective in controlling fungal pathogens like Rhizoctonia solani. To determine whether R. solani can develop SYP-14288 resistance and possibly multi-drug resistance (MDR), an SYP-14288-resistant mutant of R. solani X19-...

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Autores principales: Cheng, Xingkai, Dai, Tan, Hu, Zhihong, Cui, Tongshan, Wang, Weizhen, Han, Ping, Hu, Maolin, Hao, Jianjun, Liu, Pengfei, Liu, Xili
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977892/
https://www.ncbi.nlm.nih.gov/pubmed/35387083
http://dx.doi.org/10.3389/fmicb.2022.806339
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author Cheng, Xingkai
Dai, Tan
Hu, Zhihong
Cui, Tongshan
Wang, Weizhen
Han, Ping
Hu, Maolin
Hao, Jianjun
Liu, Pengfei
Liu, Xili
author_facet Cheng, Xingkai
Dai, Tan
Hu, Zhihong
Cui, Tongshan
Wang, Weizhen
Han, Ping
Hu, Maolin
Hao, Jianjun
Liu, Pengfei
Liu, Xili
author_sort Cheng, Xingkai
collection PubMed
description SYP-14288 is a fungicide as an uncoupler of oxidative phosphorylation, which is effective in controlling fungal pathogens like Rhizoctonia solani. To determine whether R. solani can develop SYP-14288 resistance and possibly multi-drug resistance (MDR), an SYP-14288-resistant mutant of R. solani X19-7 was generated from wild-type strain X19, and the mechanism of resistance was studied through metabolic and genetic assays. From metabolites of R. solani treated with SYP-14288, three compounds including M1, M2, and M3 were identified according to UPLC-MS/MS analysis, and M1 accumulated faster than M2 and M3 in X19-7. When X19-7 was treated by glutathione-S-transferase (GST) inhibitor diethyl maleate (DEM) and SYP-14288 together, or by DEM plus one of tested fungicides that have different modes of action, a synergistic activity of resistance occurred, implying that GSTs promoted metabolic resistance against SYP-14288 and therefore led to MDR. By comparing RNA sequences between X19-7 and X19, six cytochrome P450s (P450s) and two GST genes were selected as a target, which showed a higher expression in X19-7 than X19 both before and after the exposure to SYP-14288. Furthermore, heterologous expression of P450 and GST genes in yeast was conducted to confirm genes involved in metabolic resistance. In results, the P450 gene AG1IA_05136 and GST gene AG1IA_07383 were related to fungal resistance to multiple fungicides including SYP-14288, fluazinam, chlorothalonil, and difenoconazole. It was the first report that metabolic resistance of R. solani to uncouplers was associated with P450 and GST genes.
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spelling pubmed-89778922022-04-05 Cytochrome P450 and Glutathione S-Transferase Confer Metabolic Resistance to SYP-14288 and Multi-Drug Resistance in Rhizoctonia solani Cheng, Xingkai Dai, Tan Hu, Zhihong Cui, Tongshan Wang, Weizhen Han, Ping Hu, Maolin Hao, Jianjun Liu, Pengfei Liu, Xili Front Microbiol Microbiology SYP-14288 is a fungicide as an uncoupler of oxidative phosphorylation, which is effective in controlling fungal pathogens like Rhizoctonia solani. To determine whether R. solani can develop SYP-14288 resistance and possibly multi-drug resistance (MDR), an SYP-14288-resistant mutant of R. solani X19-7 was generated from wild-type strain X19, and the mechanism of resistance was studied through metabolic and genetic assays. From metabolites of R. solani treated with SYP-14288, three compounds including M1, M2, and M3 were identified according to UPLC-MS/MS analysis, and M1 accumulated faster than M2 and M3 in X19-7. When X19-7 was treated by glutathione-S-transferase (GST) inhibitor diethyl maleate (DEM) and SYP-14288 together, or by DEM plus one of tested fungicides that have different modes of action, a synergistic activity of resistance occurred, implying that GSTs promoted metabolic resistance against SYP-14288 and therefore led to MDR. By comparing RNA sequences between X19-7 and X19, six cytochrome P450s (P450s) and two GST genes were selected as a target, which showed a higher expression in X19-7 than X19 both before and after the exposure to SYP-14288. Furthermore, heterologous expression of P450 and GST genes in yeast was conducted to confirm genes involved in metabolic resistance. In results, the P450 gene AG1IA_05136 and GST gene AG1IA_07383 were related to fungal resistance to multiple fungicides including SYP-14288, fluazinam, chlorothalonil, and difenoconazole. It was the first report that metabolic resistance of R. solani to uncouplers was associated with P450 and GST genes. Frontiers Media S.A. 2022-03-21 /pmc/articles/PMC8977892/ /pubmed/35387083 http://dx.doi.org/10.3389/fmicb.2022.806339 Text en Copyright © 2022 Cheng, Dai, Hu, Cui, Wang, Han, Hu, Hao, Liu and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Cheng, Xingkai
Dai, Tan
Hu, Zhihong
Cui, Tongshan
Wang, Weizhen
Han, Ping
Hu, Maolin
Hao, Jianjun
Liu, Pengfei
Liu, Xili
Cytochrome P450 and Glutathione S-Transferase Confer Metabolic Resistance to SYP-14288 and Multi-Drug Resistance in Rhizoctonia solani
title Cytochrome P450 and Glutathione S-Transferase Confer Metabolic Resistance to SYP-14288 and Multi-Drug Resistance in Rhizoctonia solani
title_full Cytochrome P450 and Glutathione S-Transferase Confer Metabolic Resistance to SYP-14288 and Multi-Drug Resistance in Rhizoctonia solani
title_fullStr Cytochrome P450 and Glutathione S-Transferase Confer Metabolic Resistance to SYP-14288 and Multi-Drug Resistance in Rhizoctonia solani
title_full_unstemmed Cytochrome P450 and Glutathione S-Transferase Confer Metabolic Resistance to SYP-14288 and Multi-Drug Resistance in Rhizoctonia solani
title_short Cytochrome P450 and Glutathione S-Transferase Confer Metabolic Resistance to SYP-14288 and Multi-Drug Resistance in Rhizoctonia solani
title_sort cytochrome p450 and glutathione s-transferase confer metabolic resistance to syp-14288 and multi-drug resistance in rhizoctonia solani
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977892/
https://www.ncbi.nlm.nih.gov/pubmed/35387083
http://dx.doi.org/10.3389/fmicb.2022.806339
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