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

Populations of the causal agent of wheat tan spot, Pyrenophora tritici-repentis, that are collected from fields frequently treated with reduced fungicide concentrations have reduced sensitivity to strobilurin fungicides and azole fungicides (C(14)-demethylase inhibitors). Energy-dependent efflux transporter activity can be induced under field conditions and after in vitro application of sublethal amounts of fungicides. Efflux transporters can mediate cross-resistance to a number of fungicides that belong to different chemical classes and have different modes of action. Resistant isolates can grow on substrata amended with fungicides and can infect plants treated with fungicides at levels above recommended field concentrations. We identified the hydroxyflavone derivative 2-(4-ethoxy-phenyl)-chromen-4-one as a potent inhibitor of energy-dependent fungicide efflux transporters in P. tritici-repentis. Application of this compound in combination with fungicides shifted fungicide-resistant P. tritici-repentis isolates back to normal sensitivity levels and prevented infection of wheat leaves. These results highlight the role of energy-dependent efflux transporters in fungicide resistance and could enable a novel disease management strategy based on the inhibition of fungicide efflux to be developed

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

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

Assessment of Sensitivities to Anilinopyrimidine- and Strobilurin-fungicides in Populations of the Apple Scab Fungus Venturia inaequalis

The sensitivity of Venturia inaequalis populations to the anilinopyrimidine fungicides pyrimethanil and cyprodinil was analysed by microscopic in vivo analysis of conidiophore formation. The sensitivity to the strobilurin kresoxim-methyl was analysed using an in vitro germination assay and by determination of the diseased leaf area and conidia produced in vivo. Baseline sensitivities were determined with V. inaequalis populations from control orchards that had never been treated with fungicides. Comparison of the baseline sensitivities with sensitivities ofpopulations obtained from orchards that had received 43 anilinopyrimidine treatments over 4 years, or from an orchard with 54 kresoxim-methyl treatments over 6 years indicated that no resistance to these fungicides has developed at the sites sampled

Mecanismos e significância da resistência a fungicidas

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.A ocorrência de resistência a fungicidas é uma das mais importantes conseqüências da agricultura moderna. Este fato pode ser resultado de mutações em genes codificadores de resistência a fungicidas (resistência quantitativa) ou a diferentes mecanismos que são induzidos por stresse devido a doses subletais dos produtos utilizados. Estes mecanismos produzem diferentes e variados níveis de resistência (resistência quantitativa). Também é discutido se o uso extensivo de fungicidas em ambientes agricultáveis é relacionado ou não com a ocorrência de resistência em ambientes clínicos. Além disso, também são fornecidas recomendações de como prevenir ou mesmo retardar o desenvolvimento de resistência a fungicidas em patógenos.H.B.D'sDFG - Deutsche ForschungsgemeinschaftCNP