The drug transporter MgMfs1 can modulate sensitivity of field strains of the fungal wheat pathogen <i>Mycosphaerella graminicola</i> to the strobilurin fungicide trifloxystrobin

Roohparvar, Ramin; Mehrabi, Rahim; Nistelrooy, J.G.M. van; Zwiers, L.H.; Waard, M.A. de

doi:10.1002/ps.1569

Cited by 30 publications

(33 citation statements)

References 155 publications

(174 reference statements)

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“…In one of these populations, all strains had mutations in a zinc cluster transcription factor–encoding gene, mrr1 , causing overexpression of the ABC transporter AtrB (Kretschmer et al 2009). Resistance to sterol demethylation inhibitors and strobilurins in field isolates of Penicillium digitatum and Mycosphaerella graminicola , respectively, was also described (Nakaune et al 1998; Roohparvar et al 2008). Our work using a subtropical wild population of N. crassa (Ellison et al 2011; Palma-Guerrero et al 2013) further supports that natural variation to drug tolerance occurs and seems to be mediated by zinc cluster transcription factors.…”

Section: Discussionmentioning

confidence: 98%

CZT-1 Is a Novel Transcription Factor Controlling Cell Death and Natural Drug Resistance in Neurospora crassa

Gonçalves

Hall

Kowbel

et al. 2014

G3 Genes|Genomes|Genetics

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We pinpoint CZT-1 (cell death–activated zinc cluster transcription factor) as a novel transcription factor involved in tolerance to cell death induced by the protein kinase inhibitor staurosporine in Neurospora crassa. Transcriptional profiling of staurosporine-treated wild-type cells by RNA-sequencing showed that genes encoding the machinery for protein synthesis are enriched among the genes repressed by the drug. Functional category enrichment analyses also show that genes encoding components of the mitochondrial respiratory chain are downregulated by staurosporine, whereas genes involved in endoplasmic reticulum activities are upregulated. In contrast, a staurosporine-treated Δczt-1 deletion strain is unable to repress the genes for the respiratory chain and to induce the genes related to the endoplasmic reticulum, indicating a role for CZT-1 in the regulation of activity of these organelles. The Δczt-1 mutant strain displays increased reactive oxygen species accumulation on insult with staurosporine. A genome-wide association study of a wild population of N. crassa isolates pointed out genes associated with a cell death role of CZT-1, including catalase-1 (cat-1) and apoptosis-inducing factor–homologous mitochondrion-associated inducer of death 2 (amid-2). Importantly, differences in the expression of czt-1 correlates with resistance to staurosporine among wild isolate strains. Our results reveal a novel transcription factor that regulates drug resistance and cell death in response to staurosporine in laboratory strains as well as in wild isolates of N. crassa.

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Section: Discussionmentioning

confidence: 98%

CZT-1 Is a Novel Transcription Factor Controlling Cell Death and Natural Drug Resistance in Neurospora crassa

Gonçalves

Hall

Kowbel

et al. 2014

G3 Genes|Genomes|Genetics

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“…More recently, C. glabrata homologs of DHA1 Qdr2 (Costa et al, 2013a), Aqr1 (Costa et al, 2013b), and Tpo3 (Costa et al, 2014) have been implicated in antifungal drug resistance, while the homolog of Aqr1 and Tpo3 were further shown to have a role in acetic acid resistance and polyamine homeostasis, respectively (Costa et al, 2013b, 2014). In phytopathogenic fungi, which constitute an important problem in crop protection, MDR/MXR-MFS transporters such as BcMfs1 from Botrytis cinerea (Hayashi et al, 2002) and MgMfs1 from Mycosphaerella graminicola (Roohparvar et al, 2007, 2008) have also been shown to be involved in resistance to natural plant toxins and fungicides. Altogether, the role of many DHA transporters from fungal species was found to, at least partially, mirror their S. cerevisiae homologs, highlighting the relevance of studies in the model yeast to elucidate the regulation and functional role of these transporters in other species.…”

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

MFS transporters required for multidrug/multixenobiotic (MD/MX) resistance in the model yeast: understanding their physiological function through post-genomic approaches

Santos¹,

Teixeira²,

Dias³

et al. 2014

Front. Physiol.

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Multidrug/Multixenobiotic resistance (MDR/MXR) is a widespread phenomenon with clinical, agricultural and biotechnological implications, where MDR/MXR transporters that are presumably able to catalyze the efflux of multiple cytotoxic compounds play a key role in the acquisition of resistance. However, although these proteins have been traditionally considered drug exporters, the physiological function of MDR/MXR transporters and the exact mechanism of their involvement in resistance to cytotoxic compounds are still open to debate. In fact, the wide range of structurally and functionally unrelated substrates that these transporters are presumably able to export has puzzled researchers for years. The discussion has now shifted toward the possibility of at least some MDR/MXR transporters exerting their effect as the result of a natural physiological role in the cell, rather than through the direct export of cytotoxic compounds, while the hypothesis that MDR/MXR transporters may have evolved in nature for other purposes than conferring chemoprotection has been gaining momentum in recent years. This review focuses on the drug transporters of the Major Facilitator Superfamily (MFS; drug:H+ antiporters) in the model yeast Saccharomyces cerevisiae. New insights into the natural roles of these transporters are described and discussed, focusing on the knowledge obtained or suggested by post-genomic research. The new information reviewed here provides clues into the unexpectedly complex roles of these transporters, including a proposed indirect regulation of the stress response machinery and control of membrane potential and/or internal pH, with a special emphasis on a genome-wide view of the regulation and evolution of MDR/MXR-MFS transporters.

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“…In the budding yeast, MFS transporters containing either a 12- or 14-transmembrane domain have been demonstrated to confer resistance to a wide array of chemicals and drugs [3] and their regulation has been found to be controlled by several stress related transcription factors including Yap1, Msn2, Msn4, and Sfp1 [2]. In phytopathogenic fungi, MFS transporters have been shown to be involved in resistance to toxins and fungicides [4–8]. …”

Section: Introductionmentioning

confidence: 99%

A Major Facilitator Superfamily Transporter-Mediated Resistance to Oxidative Stress and Fungicides Requires Yap1, Skn7, and MAP Kinases in the Citrus Fungal Pathogen Alternaria alternata

Chen

Tsai

et al. 2017

PLoS ONE

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Major Facilitator Superfamily (MFS) transporters play an important role in multidrug resistance in fungi. We report an AaMFS19 gene encoding a MFS transporter required for cellular resistance to oxidative stress and fungicides in the phytopathogenic fungus Alternaria alternata. AaMFS19, containing 12 transmembrane domains, displays activity toward a broad range of substrates. Fungal mutants lacking AaMFS19 display profound hypersensitivities to cumyl hydroperoxide, potassium superoxide, many singlet oxygen-generating compounds (eosin Y, rose Bengal, hematoporphyrin, methylene blue, and cercosporin), and the cell wall biosynthesis inhibitor, Congo red. AaMFS19 mutants also increase sensitivity to copper ions, clotrimazole, fludioxonil, and kocide fungicides, 2-chloro-5-hydroxypyridine (CHP), and 2,3,5-triiodobenzoic acid (TIBA). AaMFS19 mutants induce smaller necrotic lesions on leaves of a susceptible citrus cultivar. All observed phenotypes in the mutant are restored by introducing and expressing a wild-type copy of AaMFS19. The wild-type strain of A. alternata treated with either CHP or TIBA reduces radial growth and formation and germination of conidia, increases hyphal branching, and results in decreased expression of the AaMFS19 gene. The expression of AaMFS19 is regulated by the Yap1 transcription activator, the Hog1 and Fus3 mitogen-activated protein (MAP) kinases, the ‘two component’ histidine kinase, and the Skn7 response regulator. Our results demonstrate that A. alternata confers resistance to different chemicals via a membrane-bound MFS transporter.

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The drug transporter MgMfs1 can modulate sensitivity of field strains of the fungal wheat pathogen Mycosphaerella graminicola to the strobilurin fungicide trifloxystrobin

Abstract: It is concluded that the drug transporter MgMfs1 is a determinant of strobilurin sensitivity of field strains of M. graminicola.

Cited by 30 publications

References 155 publications

CZT-1 Is a Novel Transcription Factor Controlling Cell Death and Natural Drug Resistance in Neurospora crassa

CZT-1 Is a Novel Transcription Factor Controlling Cell Death and Natural Drug Resistance in Neurospora crassa

MFS transporters required for multidrug/multixenobiotic (MD/MX) resistance in the model yeast: understanding their physiological function through post-genomic approaches

A Major Facilitator Superfamily Transporter-Mediated Resistance to Oxidative Stress and Fungicides Requires Yap1, Skn7, and MAP Kinases in the Citrus Fungal Pathogen Alternaria alternata

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