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Antimicrobial Agents and Chemotherapy, December 2002, p. 3900-3906, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3900-3906.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

ABC Transporters and Azole Susceptibility in Laboratory Strains of the Wheat Pathogen Mycosphaerella graminicola

Lute-Harm Zwiers, Ioannis Stergiopoulos, Johannes G. M. Van Nistelrooy, and Maarten A. De Waard*

Laboratory of Phytopathology, Wageningen University, 6700 EE Wageningen, The Netherlands

Received 13 May 2002/ Returned for modification 9 July 2002/ Accepted 13 September 2002

Laboratory strains of Mycosphaerella graminicola with decreased susceptibilities to the azole antifungal agent cyproconazole showed a multidrug resistance phenotype by exhibiting cross-resistance to an unrelated chemical, cycloheximide or rhodamine 6G, or both. Decreased azole susceptibility was found to be associated with either decreased or increased levels of accumulation of cyproconazole. No specific relationship could be observed between azole susceptibility and the expression of ATP-binding cassette (ABC) transporter genes MgAtr1 to MgAtr5 and the sterol P450 14{alpha}-demethylase gene, CYP51. ABC transporter MgAtr1 was identified as a determinant in azole susceptibility since heterologous expression of the protein reduced the azole susceptibility of Saccharomyces cerevisiae and disruption of MgAtr1 in one specific M. graminicola laboratory strain with constitutive MgAtr1 overexpression restored the level of susceptibility to cyproconazole to wild-type levels. However, the level of accumulation in the mutant with an MgAtr1 disruption did not revert to the wild-type level. We propose that variations in azole susceptibility in laboratory strains of M. graminicola are mediated by multiple mechanisms.

* Corresponding author. Mailing address: Laboratory of Phytopathology, Wageningen University, P.O. Box 8025, 6700 EE Wageningen, The Netherlands. Phone: 31 317 483123. Fax: 31 317 483412. E-mail: Maarten.deWaard{at}wur.nl.

Antimicrobial Agents and Chemotherapy, December 2002, p. 3900-3906, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3900-3906.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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