Division of Phytopathologie

2. Function and regulation of drug-efflux transporters

Plant pathogenic fungi are exposed to a multitude of toxic compounds. Among the various mechanisms that allow them to survive ‘toxic environments’, we are studying the role of plasma membrane drug-efflux pumps in detoxification (Fig. 3). The genome of B. cinerea encodes more than 40 ABC-type, and more than 100 putative MFS-type efflux transporters. While most of these transporters are not yet functionally characterized, some of them have been shown to be involved in the export of fungicides, antibiotics and plant defense compounds (de Waard et al., 2006). The ABC transporter AtrB1 has been shown to transport a variety of natural and synthetic drugs, including the phytoalexin of Brassicaceae, camalexin. B. cinerea mutants lacking atrB show reduced pathogenicity on Arabidopsis wild type plants, but not on camalexin-deficient mutants, indicating that AtrB helps to overcome the chemical defense of host plants (Stefanato et al., 2009). Transcription of atrB is induced by various drugs, and requires the zinc cluster transcription factor Mrr1. We have identified a variety of gain-of-function mutations in mrr1 that lead to permanent activation of Mrr1, resulting in constitutive overexpression of atrB and multidrug resistance (MDR) phenotypes (see below; Kretschmer et al., 2009). We are further investigating the molecular details of expression regulation of drug efflux transporters (Fig. 4), and their role in protection of B. cinerea against chemical stress. A model for the regulation of expression of atrB by Mrr1 is shown in Fig. 5.

Literature

De Waard MA, Andrade AC, Hayashi K, Schoonbeek HJ, Stergiopoulos I, Zwiers LH (2006). Impact of fungal drug transporters on fungicide sensitivity, multidrug resistance and virulence. Pest Manag. Sci. 62: 195–207.

Kretschmer M, Leroch M, Mosbach A, Walker A-S, Fillinger S, Mernke D, Schoonbeek H-J, Pradier J-M, Leroux P, De Waard MA, Hahn M (2009). Fungicide-driven evolution and molecular Basis of Multidrug Resistance in Field Populations of the Grey Mould Fungus Botrytis cinerea. PLoS Pathog 5(12): e1000696.

Stefanato F, Abou-Mansour E, Buchala A, Kretschmer M, Mosbach A, Hahn M, Bochet C, Metraux J-P, Schoonbeek H-J (2009). The ABC-transporter BcatrB from Botrytis cinerea exports camalexin and is a virulence factor on Arabidopsis thaliana. The Plant Journal 58: 499-510

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