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C239S Mutation in the β-Tubulin of Phytophthora sojae Confers Resistance to Zoxamide

Zoxamide is the sole β-tubulin inhibitor registered for the control of oomycete pathogens. The current study investigated the activity of zoxamide against Phytophthora sojae and baseline sensitivity was established with a mean EC(50) of 0.048 μg/ml. The data is critical for monitoring changes in zox...

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Autores principales: Cai, Meng, Miao, Jianqiang, Song, Xi, Lin, Dong, Bi, Yang, Chen, Lei, Liu, Xili, Tyler, Brett M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873504/
https://www.ncbi.nlm.nih.gov/pubmed/27242773
http://dx.doi.org/10.3389/fmicb.2016.00762
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author Cai, Meng
Miao, Jianqiang
Song, Xi
Lin, Dong
Bi, Yang
Chen, Lei
Liu, Xili
Tyler, Brett M.
author_facet Cai, Meng
Miao, Jianqiang
Song, Xi
Lin, Dong
Bi, Yang
Chen, Lei
Liu, Xili
Tyler, Brett M.
author_sort Cai, Meng
collection PubMed
description Zoxamide is the sole β-tubulin inhibitor registered for the control of oomycete pathogens. The current study investigated the activity of zoxamide against Phytophthora sojae and baseline sensitivity was established with a mean EC(50) of 0.048 μg/ml. The data is critical for monitoring changes in zoxamide-sensitivity in the field. Three stable resistant mutants with a high resistance level were obtained by selection on zoxamide amended media. Although the development of resistance occurred at a low frequency, there were no apparent fitness penalty in the acquired mutants in terms of growth rate, sporulation, germination and pathogenicity. Based on the biological profiles and low mutagenesis rate, the resistance risk of P. sojae to zoxamide can be estimated as low to medium. Further investigation revealed all the zoxamide-resistant mutants had a point mutation of C239S in their β-tubulin. Zoxamide also exhibited high activity against most species from the genus Pythium in which only Pythium aphanidermatum was found naturally resistant to zoxamide and harboring the natural point mutation S239 in the β-tubulin. Back-transformation in P. sojae with the mutated allele (S239) confirmed the C239S mutation can induce resistance to zoxamide, and the resistance level was positively related to the expression level of the mutated gene. In contrast, the overexpression of the wild type gene was unable to cause zoxamide resistance. It is the first report on the resistance molecular mechanism of zoxamide in oomycetes. Based on our study, C239 is supposed to be a key target site of zoxamide, which distinguishes zoxamide from benzimidazoles and accounts for its low resistance risk. The result can provide advice on the design of new β-tubulin inhibitors in future.
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spelling pubmed-48735042016-05-30 C239S Mutation in the β-Tubulin of Phytophthora sojae Confers Resistance to Zoxamide Cai, Meng Miao, Jianqiang Song, Xi Lin, Dong Bi, Yang Chen, Lei Liu, Xili Tyler, Brett M. Front Microbiol Microbiology Zoxamide is the sole β-tubulin inhibitor registered for the control of oomycete pathogens. The current study investigated the activity of zoxamide against Phytophthora sojae and baseline sensitivity was established with a mean EC(50) of 0.048 μg/ml. The data is critical for monitoring changes in zoxamide-sensitivity in the field. Three stable resistant mutants with a high resistance level were obtained by selection on zoxamide amended media. Although the development of resistance occurred at a low frequency, there were no apparent fitness penalty in the acquired mutants in terms of growth rate, sporulation, germination and pathogenicity. Based on the biological profiles and low mutagenesis rate, the resistance risk of P. sojae to zoxamide can be estimated as low to medium. Further investigation revealed all the zoxamide-resistant mutants had a point mutation of C239S in their β-tubulin. Zoxamide also exhibited high activity against most species from the genus Pythium in which only Pythium aphanidermatum was found naturally resistant to zoxamide and harboring the natural point mutation S239 in the β-tubulin. Back-transformation in P. sojae with the mutated allele (S239) confirmed the C239S mutation can induce resistance to zoxamide, and the resistance level was positively related to the expression level of the mutated gene. In contrast, the overexpression of the wild type gene was unable to cause zoxamide resistance. It is the first report on the resistance molecular mechanism of zoxamide in oomycetes. Based on our study, C239 is supposed to be a key target site of zoxamide, which distinguishes zoxamide from benzimidazoles and accounts for its low resistance risk. The result can provide advice on the design of new β-tubulin inhibitors in future. Frontiers Media S.A. 2016-05-20 /pmc/articles/PMC4873504/ /pubmed/27242773 http://dx.doi.org/10.3389/fmicb.2016.00762 Text en Copyright © 2016 Cai, Miao, Song, Lin, Bi, Chen, Liu and Tyler. http://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) or licensor 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
Cai, Meng
Miao, Jianqiang
Song, Xi
Lin, Dong
Bi, Yang
Chen, Lei
Liu, Xili
Tyler, Brett M.
C239S Mutation in the β-Tubulin of Phytophthora sojae Confers Resistance to Zoxamide
title C239S Mutation in the β-Tubulin of Phytophthora sojae Confers Resistance to Zoxamide
title_full C239S Mutation in the β-Tubulin of Phytophthora sojae Confers Resistance to Zoxamide
title_fullStr C239S Mutation in the β-Tubulin of Phytophthora sojae Confers Resistance to Zoxamide
title_full_unstemmed C239S Mutation in the β-Tubulin of Phytophthora sojae Confers Resistance to Zoxamide
title_short C239S Mutation in the β-Tubulin of Phytophthora sojae Confers Resistance to Zoxamide
title_sort c239s mutation in the β-tubulin of phytophthora sojae confers resistance to zoxamide
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873504/
https://www.ncbi.nlm.nih.gov/pubmed/27242773
http://dx.doi.org/10.3389/fmicb.2016.00762
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