title: Two promoter rearrangements in a drug efflux transporter gene are responsible for the appearance and spread of multidrug resistance phenotype MDR2 in Botrytis cinerea isolates in French and German vineyards.
abstract: In French and German vineyards, Botrytis cinerea isolates with multiple fungicide resistance phenotypes have been observed with increasing frequencies. Multidrug resistance (MDR) results from mutations that lead to constitutive overexpression of genes encoding drug efflux transporters. In MDR2 and MDR3 strains, overexpression of the major facilitator superfamily transporter gene mfsM2 has been found to result from a rearrangement in the mfsM2 promoter (type A), caused by insertion of a retroelement (RE)-derived sequence. Here, we report the discovery of another, similar RE-induced rearrangement of the mfsM2 promoter (type B) in a subpopulation of French MDR2 isolates. MDR2 isolates harboring either type A or type B mutations in mfsM2 show the same resistance phenotypes and similar levels of mfsM2 overexpression. RE sequences similar to those in mfsM2 were found in low copy numbers in other but not all B. cinerea strains analyzed, including non-MDR2 strains. Population genetic analyses support the hypothesis that the two rearrangement mutations have only occurred once, and are responsible for the appearance and subsequent spread of all known MDR2 and MDR3 strains in French and German wine-growing regions.
authors.affiliation: University of Kaiserslautern, Department of Biology, Kaiserslautern, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Mernke
authors.forename: S
authors.initials: S
authors.lastname: Dahm
authors.forename: A-S
authors.initials: AS
authors.lastname: Walker
authors.forename: A
authors.initials: A
authors.lastname: Lalève
authors.forename: S
authors.initials: S
authors.lastname: Fillinger
authors.forename: M
authors.initials: M
authors.lastname: Leroch
authors.forename: M
authors.initials: M
authors.lastname: Hahn
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D020171:Botrytis / Q000187:drug effects* / Q000235:genetics*; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics*; D005602:France; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005659:Fungicides, Industrial / Q000494:pharmacology; D015321:Gene Rearrangement; D005828:Genetics, Population; D005858:Germany; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics; D018626:Retroelements / Q000235:genetics; D017422:Sequence Analysis, DNA; D027843:Vitis / Q000382:microbiology*; D014920:Wine / Q000382:microbiology; D000097202:ATP-Binding Cassette Sub-Family B Member 4
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D005656:Fungal Proteins; D005659:Fungicides, Industrial; D018626:Retroelements; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C095122:multidrug resistance protein 3