Multidrug Resistance in Botrytis cinerea Associated with Decreased Accumulation of the Azole Fungicide Oxpoconazole and Increased Transcription of the ABC Transporter Gene BcatrD

Hayashi, Keisuke; Schoonbeek, Henk‐jan; Sugiura, Hisao; Waard, M.A. de

doi:10.1006/pest.2001.2548

Cited by 71 publications

(59 citation statements)

References 36 publications

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“…BcatrB is not a DMI transporter (29,33). Still, expression of BcatrB is induced by treatment with DMI fungicides (16), indicating that inducers of expression of BcatrB are not necessarily a substrate of the encoded proteins. Similar phenomena have been described for other ABC genes (17,29).…”

Section: Discussionmentioning

confidence: 96%

“…6), which suggests that efflux activity still proceeds to a weak extent. The transporter gene involved might be BcatrG and/or BcatrK, since expression of these genes was induced by DMI fungicides (16). Such a situation would indicate that multiple transporter proteins mediate the transport of a particular compound.…”

Section: Discussionmentioning

confidence: 99%

“…Recently we demonstrated that B. cinerea possesses multiple ABC and MFS transporter genes (16,33) and showed that the ABC transporter BcatrB plays a role in protection against the plant defense compound resveratrol and phenylpyrrole fungicides (29). Similarly, the ABC transporter BcatrD provides protection against DMIs (17).…”

mentioning

confidence: 99%

“…Similarly, the ABC transporter BcatrD provides protection against DMIs (17). Overexpression of these transporters in laboratory-generated mutants resulted in multidrug resistance to fungicides and unrelated chemicals (16). This mechanism may also apply to fungicide resistance development under field conditions (7,19).…”

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confidence: 99%

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Bcmfs1 , a Novel Major Facilitator Superfamily Transporter from Botrytis cinerea , Provides Tolerance towards the Natural Toxic Compounds Camptothecin and Cercosporin and towards Fungicides

Hayashi

Schoonbeek

Waard

2002

Appl Environ Microbiol

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124

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Bcmfs1, a novel major facilitator superfamily gene from Botrytis cinerea, was cloned, and replacement and overexpression mutants were constructed to study its function. Replacement mutants showed increased sensitivity to the natural toxic compounds camptothecin and cercosporin, produced by the plant Camptotheca acuminata and the plant pathogenic fungus Cercospora kikuchii, respectively. Overexpression mutants displayed decreased sensitivity to these compounds and to structurally unrelated fungicides, such as sterol demethylation inhibitors (DMIs). A double-replacement mutant of Bcmfs1 and the ATP-binding cassette (ABC) transporter gene BcatrD was more sensitive to DMI fungicides than a single-replacement mutant of BcatrD, known to encode an important ABC transporter of DMIs. The sensitivity of the wild-type strain and mutants to DMI fungicides correlated with Bcmfs1 expression levels and with the initial accumulation of oxpoconazole by germlings of these isolates. The results indicate that Bcmfs1 is a major facilitator superfamily multidrug transporter involved in protection against natural toxins and fungicides and has a substrate specificity that overlaps with the ABC transporter BcatrD. Bcmfs1 may be involved in protection of B. cinerea against plant defense compounds during the pathogenic phase of growth on host plants and against fungitoxic antimicrobial metabolites during its saprophytic phase of growth.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Bcmfs1 , a Novel Major Facilitator Superfamily Transporter from Botrytis cinerea , Provides Tolerance towards the Natural Toxic Compounds Camptothecin and Cercosporin and towards Fungicides

Hayashi

Schoonbeek

Waard

2002

Appl Environ Microbiol

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124

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“…Currently, the most widespread hypothesis to explain the reduced levels of toxic products in the cell is based on active efflux of these compounds by ABC transporters (ATP binding cassette) and MFS (Major Facilitator Superfamily) (Hayashi et al, 2001(Hayashi et al, , 2002a(Hayashi et al, , 2002b(Hayashi et al, , 2003Stergiopoulos et al, 2002aStergiopoulos et al, , 2002bStergiopoulos & de Waard, 2002, Vermeulen et al, 2001. ABC and MFS transporters are the most studied so far and have been described in many fungi such as Aspergillus nidulans, Botrytis cinerea, Mycosphaerella graminicola, Magnaporthe grisea, Penicillium digitatum, etc (Andrade et al, 2000a, 2000bdel Sorbo et al, 2000;Nakaune, 2001;Schoonbeek et al, 2003;Stergiopoulos et al, 2002a;Stergiopoulos & de Waard, 2002;Vermeulen et al, 2001;Yoder and Turgeon 2001;Zwiers et al, 2003).…”

Section: The Reduction Of Intracellular Concentration Of Antifungal Cmentioning

confidence: 99%

Molecular Tools for Detection of Plant Pathogenic Fungi and Fungicide Resistance

Capote¹,

Pastrana²,

Aguado³

et al. 2012

Plant Pathology

107

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Impact of fungal drug transporters on fungicide sensitivity, multidrug resistance and virulence

Waard

Andrade

Hayashi

et al. 2006

Pest Management Science

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177

178

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Drug transporters are membrane proteins that provide protection for organisms against natural toxic products and fungicides. In plant pathogens, drug transporters function in baseline sensitivity to fungicides, multidrug resistance (MDR) and virulence on host plants. This paper describes drug transporters of the filamentous fungi Aspergillus nidulans (Eidam) Winter, Botrytis cinerea Pers and Mycosphaerella graminicola (Fückel) Schroter that function in fungicide sensitivity and resistance. The fungi possess ATP-binding cassette (ABC) drug transporters that mediate MDR to fungicides in laboratory mutants. Similar mutants are not pronounced in field resistance to most classes of fungicide but may play a role in resistance to azoles. MDR may also explain historical cases of resistance to aromatic hydrocarbon fungicides and dodine. In clinical situations, MDR development in Candida albicans (Robin) Berkhout mediated by ABC transporters in patients suffering from candidiasis is common after prolonged treatment with azoles. Factors that can explain this striking difference between agricultural and clinical situations are discussed. Attention is also paid to the risk of MDR development in plant pathogens in the future. Finally, the paper describes the impact of fungal drug transporters on drug discovery.

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Multidrug Resistance in Botrytis cinerea Associated with Decreased Accumulation of the Azole Fungicide Oxpoconazole and Increased Transcription of the ABC Transporter Gene BcatrD

Cited by 71 publications

References 36 publications

Bcmfs1 , a Novel Major Facilitator Superfamily Transporter from Botrytis cinerea , Provides Tolerance towards the Natural Toxic Compounds Camptothecin and Cercosporin and towards Fungicides

Bcmfs1 , a Novel Major Facilitator Superfamily Transporter from Botrytis cinerea , Provides Tolerance towards the Natural Toxic Compounds Camptothecin and Cercosporin and towards Fungicides

Molecular Tools for Detection of Plant Pathogenic Fungi and Fungicide Resistance

Impact of fungal drug transporters on fungicide sensitivity, multidrug resistance and virulence

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