Plasticity of the <italic toggle="yes">MFS1</italic> Promoter Leads to Multidrug Resistance in the Wheat Pathogen <italic toggle="yes">Zymoseptoria tritici</italic>
ABSTRACT The ascomycete Zymoseptoria tritici is the causal agent of Septoria leaf blotch on wheat. Disease control relies mainly on resistant wheat cultivars and on fungicide applications. The fungus displays a high potential to circumvent both methods. Resistance against all unisite fungicides has...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2017-10-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00393-17 |
| _version_ | 1819041664111476736 |
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| author | Selim Omrane Colette Audéon Amandine Ignace Clémentine Duplaix Lamia Aouini Gert Kema Anne-Sophie Walker Sabine Fillinger |
| author_facet | Selim Omrane Colette Audéon Amandine Ignace Clémentine Duplaix Lamia Aouini Gert Kema Anne-Sophie Walker Sabine Fillinger |
| author_sort | Selim Omrane |
| collection | DOAJ |
| description | ABSTRACT The ascomycete Zymoseptoria tritici is the causal agent of Septoria leaf blotch on wheat. Disease control relies mainly on resistant wheat cultivars and on fungicide applications. The fungus displays a high potential to circumvent both methods. Resistance against all unisite fungicides has been observed over decades. A different type of resistance has emerged among wild populations with multidrug-resistant (MDR) strains. Active fungicide efflux through overexpression of the major facilitator gene MFS1 explains this emerging resistance mechanism. Applying a bulk-progeny sequencing approach, we identified in this study a 519-bp long terminal repeat (LTR) insert in the MFS1 promoter, a relic of a retrotransposon cosegregating with the MDR phenotype. Through gene replacement, we show the insert as a mutation responsible for MFS1 overexpression and the MDR phenotype. Besides this type I insert, we found two different types of promoter inserts in more recent MDR strains. Type I and type II inserts harbor potential transcription factor binding sites, but not the type III insert. Interestingly, all three inserts correspond to repeated elements present at different genomic locations in either IPO323 or other Z. tritici strains. These results underline the plasticity of repeated elements leading to fungicide resistance in Z. tritici and which contribute to its adaptive potential. IMPORTANCE Disease control through fungicides remains an important means to protect crops from fungal diseases and to secure the harvest. Plant-pathogenic fungi, especially Zymoseptoria tritici, have developed resistance against most currently used active ingredients, reducing or abolishing their efficacy. While target site modification is the most common resistance mechanism against single modes of action, active efflux of multiple drugs is an emerging phenomenon in fungal populations reducing additionally fungicides’ efficacy in multidrug-resistant strains. We have investigated the mutations responsible for increased drug efflux in Z. tritici field strains. Our study reveals that three different insertions of repeated elements in the same promoter lead to multidrug resistance in Z. tritici. The target gene encodes the membrane transporter MFS1 responsible for drug efflux, with the promoter inserts inducing its overexpression. These results underline the plasticity of repeated elements leading to fungicide resistance in Z. tritici. |
| first_indexed | 2024-12-21T09:28:35Z |
| format | Article |
| id | doaj.art-77e8f915e26d407581fe553b0bd3fda9 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-21T09:28:35Z |
| publishDate | 2017-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-77e8f915e26d407581fe553b0bd3fda92022-12-21T19:08:49ZengAmerican Society for MicrobiologymSphere2379-50422017-10-012510.1128/mSphere.00393-17Plasticity of the <italic toggle="yes">MFS1</italic> Promoter Leads to Multidrug Resistance in the Wheat Pathogen <italic toggle="yes">Zymoseptoria tritici</italic>Selim Omrane0Colette Audéon1Amandine Ignace2Clémentine Duplaix3Lamia Aouini4Gert Kema5Anne-Sophie Walker6Sabine Fillinger7UMR BIOGER, INRA, AgroParisTech, Université Paris-Saclay, Thiverval-Grignon, FranceUMR BIOGER, INRA, AgroParisTech, Université Paris-Saclay, Thiverval-Grignon, FranceUMR BIOGER, INRA, AgroParisTech, Université Paris-Saclay, Thiverval-Grignon, FranceUMR BIOGER, INRA, AgroParisTech, Université Paris-Saclay, Thiverval-Grignon, FranceWageningen University, Plant Research International, Wageningen, The NetherlandsWageningen University, Plant Research International, Wageningen, The NetherlandsUMR BIOGER, INRA, AgroParisTech, Université Paris-Saclay, Thiverval-Grignon, FranceUMR BIOGER, INRA, AgroParisTech, Université Paris-Saclay, Thiverval-Grignon, FranceABSTRACT The ascomycete Zymoseptoria tritici is the causal agent of Septoria leaf blotch on wheat. Disease control relies mainly on resistant wheat cultivars and on fungicide applications. The fungus displays a high potential to circumvent both methods. Resistance against all unisite fungicides has been observed over decades. A different type of resistance has emerged among wild populations with multidrug-resistant (MDR) strains. Active fungicide efflux through overexpression of the major facilitator gene MFS1 explains this emerging resistance mechanism. Applying a bulk-progeny sequencing approach, we identified in this study a 519-bp long terminal repeat (LTR) insert in the MFS1 promoter, a relic of a retrotransposon cosegregating with the MDR phenotype. Through gene replacement, we show the insert as a mutation responsible for MFS1 overexpression and the MDR phenotype. Besides this type I insert, we found two different types of promoter inserts in more recent MDR strains. Type I and type II inserts harbor potential transcription factor binding sites, but not the type III insert. Interestingly, all three inserts correspond to repeated elements present at different genomic locations in either IPO323 or other Z. tritici strains. These results underline the plasticity of repeated elements leading to fungicide resistance in Z. tritici and which contribute to its adaptive potential. IMPORTANCE Disease control through fungicides remains an important means to protect crops from fungal diseases and to secure the harvest. Plant-pathogenic fungi, especially Zymoseptoria tritici, have developed resistance against most currently used active ingredients, reducing or abolishing their efficacy. While target site modification is the most common resistance mechanism against single modes of action, active efflux of multiple drugs is an emerging phenomenon in fungal populations reducing additionally fungicides’ efficacy in multidrug-resistant strains. We have investigated the mutations responsible for increased drug efflux in Z. tritici field strains. Our study reveals that three different insertions of repeated elements in the same promoter lead to multidrug resistance in Z. tritici. The target gene encodes the membrane transporter MFS1 responsible for drug efflux, with the promoter inserts inducing its overexpression. These results underline the plasticity of repeated elements leading to fungicide resistance in Z. tritici.https://journals.asm.org/doi/10.1128/mSphere.00393-17antifungal resistancebulk progeny analysisefflux pumpsmultidrug resistancerepeated elementstranscriptional regulation |
| spellingShingle | Selim Omrane Colette Audéon Amandine Ignace Clémentine Duplaix Lamia Aouini Gert Kema Anne-Sophie Walker Sabine Fillinger Plasticity of the <italic toggle="yes">MFS1</italic> Promoter Leads to Multidrug Resistance in the Wheat Pathogen <italic toggle="yes">Zymoseptoria tritici</italic> mSphere antifungal resistance bulk progeny analysis efflux pumps multidrug resistance repeated elements transcriptional regulation |
| title | Plasticity of the <italic toggle="yes">MFS1</italic> Promoter Leads to Multidrug Resistance in the Wheat Pathogen <italic toggle="yes">Zymoseptoria tritici</italic> |
| title_full | Plasticity of the <italic toggle="yes">MFS1</italic> Promoter Leads to Multidrug Resistance in the Wheat Pathogen <italic toggle="yes">Zymoseptoria tritici</italic> |
| title_fullStr | Plasticity of the <italic toggle="yes">MFS1</italic> Promoter Leads to Multidrug Resistance in the Wheat Pathogen <italic toggle="yes">Zymoseptoria tritici</italic> |
| title_full_unstemmed | Plasticity of the <italic toggle="yes">MFS1</italic> Promoter Leads to Multidrug Resistance in the Wheat Pathogen <italic toggle="yes">Zymoseptoria tritici</italic> |
| title_short | Plasticity of the <italic toggle="yes">MFS1</italic> Promoter Leads to Multidrug Resistance in the Wheat Pathogen <italic toggle="yes">Zymoseptoria tritici</italic> |
| title_sort | plasticity of the italic toggle yes mfs1 italic promoter leads to multidrug resistance in the wheat pathogen italic toggle yes zymoseptoria tritici italic |
| topic | antifungal resistance bulk progeny analysis efflux pumps multidrug resistance repeated elements transcriptional regulation |
| url | https://journals.asm.org/doi/10.1128/mSphere.00393-17 |
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