Inhibition of Efflux Transporter-Mediated Fungicide Resistance in
            <i>Pyrenophora tritici-repentis</i>
            by a Derivative of 4′-Hydroxyflavone and Enhancement of Fungicide Activity

Reimann, Sven; Deising, H. B.

doi:10.1128/aem.71.6.3269-3275.2005

Cited by 82 publications

(52 citation statements)

References 42 publications

(52 reference statements)

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“…Fungicide-adapted (resistant) isolates were not only able to grow on artificial substrata amended with fungicides, but could also infect plants treated with fungicides at levels above recommended field concentrations. Importantly, application of the hydroxyflavone derivative 2-(4-ethoxy-phenyl)-chromen-4-one, a potent inhibitor of energy-dependent fungicide efflux transporters in P. triticirepentis, in combination with fungicides shifted fungicide resistant P. tritici-repentis isolates back to normal sensitivity levels and prevented infection of wheat leaves (41). These results clearly demonstrated the role of efflux transporters in fungicide resistance of the wheat tan spot fungus.…”

Section: Efflux Transporters Allow Fungi To Grow In the Presence Of Fsupporting

confidence: 48%

“…Due to their broad substrate specificity, the activity of the transporters can be visualized by using fluorescent dyes such as ethidium bromide or Hoechst 33342. This simple microscopic evaluation of hyphae allows assessing the efflux pump-mediated state of fungicide resistance (41). In strains that had not been adapted and were thus sensitive to fungicides, the dye invaded the hyphae and nuclear fluorescence occurred.…”

Section: Efflux Transporters Allow Fungi To Grow In the Presence Of Fmentioning

confidence: 99%

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Mechanisms and significance of fungicide resistance

Deising¹,

Reimann²,

Pascholati³

2008

Braz. J. Microbiol.

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186

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In this review article, we show that occurrence of fungicide resistance is one of the most important issues in modern agriculture. Fungicide resistance may be due to mutations of genes encoding fungicide targets (qualitative fungicide resistance) or to different mechanisms that are induced by sub-lethal fungicide stress. These mechanisms result in different and varying levels of resistance (quantitative fungicide resistance). We discuss whether or not extensive use of fungicides in agricultural environments is related to the occurrence of fungicide resistance in clinical environments. Furthermore, we provide recommendations of how development of fungicide resistant pathogen populations may be prevented or delayed.

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Section: Efflux Transporters Allow Fungi To Grow In the Presence Of Fsupporting

confidence: 48%

Section: Efflux Transporters Allow Fungi To Grow In the Presence Of Fmentioning

confidence: 99%

Mechanisms and significance of fungicide resistance

Deising¹,

Reimann²,

Pascholati³

2008

Braz. J. Microbiol.

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186

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“…Molecular mechanisms leading to DMI resistance have been studied in several important plant fungal pathogens. Common mechanisms include mutations in the target gene CYP51 (6,7), overexpression of the CYP51 gene (10,14,30), and energy-dependent drug efflux mechanisms (11,18,20,24).…”

mentioning

confidence: 99%

The Cytochrome P450 Lanosterol 14α-Demethylase Gene Is a Demethylation Inhibitor Fungicide Resistance Determinant in Monilinia fructicola Field Isolates from Georgia

Luo

Schnabel

2008

Appl Environ Microbiol

133

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Resistance in Monilinia fructicola to demethylation inhibitor (DMI) fungicides is beginning to emerge in North America, but its molecular basis is unknown. Two potential genetic determinants of DMI fungicide resistance including the 14␣-demethylase gene (MfCYP51) and the ATP-binding cassette transporter gene MfABC1, were investigated in six resistant (DMI-R) and six sensitive (DMI-S) field isolates. No point mutations leading to an amino acid change were found in the MfCYP51 gene. The constitutive expression of the MfCYP51 gene in DMI-R isolates was significantly higher compared to DMI-S isolates. Gene expression was not induced in mycelium of DMI-R or DMI-S isolates treated with 0.3 g of propiconazole/ml. A slightly higher average MfCYP51 copy number value was detected in DMI-R isolates (1.35) compared to DMI-S isolates (1.13); however, this difference could not be verified in Southern hybridization experiments or explain the up to 11-fold-increased MfCYP51 mRNA levels in DMI-R isolates. Analysis of the upstream nucleotide sequence of the MfCYP51 gene revealed a unique 65-bp repetitive element at base pair position ؊117 from the translational start site in DMI-R isolates but not in DMI-S isolates. This repetitive element contained a putative promoter and was named Mona. The link between Mona and the DMI resistance phenotype became even more apparent after studying the genetic diversity between the isolates. In contrast to DMI-S isolates, DMI-R isolates contained an MfCYP51 gene of identical nucleotide sequence associated with Mona. Still, DMI-R isolates were not genetically identical as revealed by Microsatellite-PCR analysis. Also, real-time PCR analysis of genomic DNA indicated that the relative copy number of Mona among DMI-S and DMI-R isolates varied, suggesting its potential for mobility. Interestingly, constitutive expression of the MfABC1 gene in DMI-R isolates was slightly lower than that of DMI-S isolates, but expression of the MfABC1 gene in DMI-R isolates was induced in mycelium after propiconazole treatment. Therefore, the MfABC1 gene may play a minor role in DMI fungicide resistance in M. fructicola. Our results strongly suggest that overexpression of the MfCYP51 gene is an important mechanism in conferring DMI fungicide resistance in M. fructicola field isolates from Georgia and that this overexpression is correlated with Mona located upstream of the MfCYP51 gene.

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“…Light microscopy was performed with a Nikon Eclipse 600 epifluorescence microscope (Nikon GmbH, Düsseldorf, Germany) as described previously (21). The fluorescence dye FUN-1 (Invitrogen GmbH, Karlsruhe, Germany) was used for viability assays (14).…”

Section: Methodsmentioning

confidence: 99%

“…Analyses of confidence intervals (␣ ϭ 0.05), logit transformation, and linear regression were done as described previously (21).…”

Section: Methodsmentioning

confidence: 99%

Treatment of a Clinically Relevant Plant-Pathogenic Fungus with an Agricultural Azole Causes Cross-Resistance to Medical Azoles and Potentiates Caspofungin Efficacy

Serfling

Wohlrab

Deising

2007

Antimicrob Agents Chemother

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Azoles are extensively applied in agriculture and medicine, and a relationship between the development of azole resistance in agriculture and the development of azole resistance in clinical practice may exist. The maize pathogen Colletotrichum graminicola, causing cutaneous mycosis and keratitis, has been used to investigate the acquisition of resistance to an agricultural azole and the resulting cross-resistance to various medical antifungal agents. Azole-adapted strains were less sensitive to all azoles tested but showed increased sensitivity to caspofungin, amphotericin B, and nystatin. Viability staining and infection assays with excised human skin confirmed these data.Five plant-pathogenic Colletotrichum species, including Colletotrichum graminicola, have been reported to cause cutaneous phaeohyphomycosis and keratitis in humans and are of clinical relevance (2,8,9). Most Colletotrichum crassipes, C. gloeosporioides, C. coccodes, and C. dematium strains isolated from infected tissue displayed a major degree of resistance to all azoles tested (3).In modern agriculture, Colletotrichum species have been implicated in anthracnose plant diseases worldwide, with substantial economical losses (7). Among other antifungal agents, azoles have been used extensively to control Colletotrichum species (12). Azoles differing in structure but exhibiting the same mode of action are used to treat both fungal diseases of plants and medical mycoses. As keratitis caused by Colletotrichum infection occurs primarily after injury by plant material (8,9,19), it is tempting to speculate that azole-resistant strains isolated from human tissues may have developed in fungicidetreated fields (see the report on azole resistance published by the scientific steering committee of the European Commission [http://ec.europa.eu/food/fs/sc/ssc/out278_en.pdf]). As Colletotrichum species are exposed to azoles in agricultural environments and are of clinical relevance, these pathogens are well suited to investigate the acquisition of resistance to agricultural azoles and the resulting cross-resistance to antifungal agents of various different chemical classes and modes of action used in medicine. MATERIALS AND METHODSCultivation of C. graminicola and adaptation to tebuconazole. Wild-type C. graminicola isolate CgM2 was cultivated as described previously (24).To adapt C. graminicola to tebuconazole, 1 ϫ 10 6 conidia were inoculated into 50 ml complete medium (CM) (15) and incubated in darkness at 23°C for 7 days. Cultures were then transferred into fresh liquid CM with increasing tebuconazole concentrations (1 g ml Ϫ1 for 24 h, 5 g ml Ϫ1 for 96 h, and 20 g ml Ϫ1 for 1 h). The mycelium was blended (Ultra Turrax; IKA Labortechnik, Staufen, Germany) at level 5 for 30 s, further cultivated on solidified CM containing 5 g tebuconazole ml Ϫ1 and 8 g tebuconazole ml Ϫ1 for 4 weeks each, and maintained on CM plates containing 30 g tebuconazole ml Ϫ1 . Quantitative determination of drug sensitivity. Radial growth rates of nonadapted and matched, adapted isol...

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Inhibition of Efflux Transporter-Mediated Fungicide Resistance in Pyrenophora tritici-repentis by a Derivative of 4′-Hydroxyflavone and Enhancement of Fungicide Activity

Cited by 82 publications

References 42 publications

Mechanisms and significance of fungicide resistance

Mechanisms and significance of fungicide resistance

The Cytochrome P450 Lanosterol 14α-Demethylase Gene Is a Demethylation Inhibitor Fungicide Resistance Determinant in Monilinia fructicola Field Isolates from Georgia

Treatment of a Clinically Relevant Plant-Pathogenic Fungus with an Agricultural Azole Causes Cross-Resistance to Medical Azoles and Potentiates Caspofungin Efficacy

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