Amino acid alterations in the benA (β‐tubulin) gene of Aspergillus nidulans that confer benomyl resistance

Abstract

We report the cloning and sequencing of 18 mutant alleles of the benA, beta-tubulin gene of Aspergillus nidulans that confer resistance to the benzimidazole antifungal, antimicrotubule compounds benomyl, carbendazim, nocodazole, and thiabendazole. In 12 cases, amino acid 6 was changed from histidine to tyrosine or leucine. In four cases, amino acid 198 was changed from glutamic acid to aspartic acid, glutamine, or lysine. In two cases, amino acid 200 was altered from phenylalanine to tyrosine. These data, along with previous data indicating that amino acid 165 is involved in the binding of the R2 group of these compounds [Jung and Oakley, 1990: Cell Motil. Cytoskeleton 17:87-94], suggest that regions of beta-tubulin containing amino acids 6, 165, and 198-200 interact to form the binding site of benzimidazole antimicrotubule agents. These results also suggest that the presence of phenylalanine at amino acid 200 contributes to the great sensitivity of many fungi to benzimidazole antimicrotubule agents.

Detection and characterization of carbendazim resistance in Sclerotinia sclerotiorum isolates from oilseed rape in Anhui Province of China

“…This indicates that the mutation in the β-tubulin gene might be associated with high MBC resistance in S. sclerotiorum isolates. Although a similar mechanism has been reported in other fungi, such as Botrytis cinerea (Yarden and Katan, 1993), Venturia inaequelis (Koenraadt et al, 1992) , Aspergillus nidulans (Jung et al, 1992) and Neurospora crassa (Koenraadt and Jones, 1993), this is the first report of its occurrence in S. sclerotiorum isolates on oilseed rape. As the β-tubulin gene has been fully cloned and sequenced, we can quickly detect the presence of highly resistant groups and monitor their development in the field by a specific PCR assay.…”

Sensitivity of Colletotrichum spp. Isolated from Grapes in Korea to Carbendazim and the Mixture of Carbendazim Plus Diethofencarb

“…Resistance to BEN fungicides could be conferred by single amino acid substitutions in the β-tubulin molecule (Jung et al, 1992). Our results suggested that the substitution of tyrosine for phenylalanine at amino acid residue 200 conferred resistance to MBC and to the mixture in 12 isolates of C. gloeosporioides.…”

“…Our results suggested that the substitution of tyrosine for phenylalanine at amino acid residue 200 conferred resistance to MBC and to the mixture in 12 isolates of C. gloeosporioides. With regard to the relationship between a substitution of amino acid in β-tubulin and resistant phenotypes, the polar hydroxy (OH) group of the tyrosine at amino acid 200 might interfere with binding to the BEN fungicide, resulting in BEN resistance (Jung et al, 1992).…”

Kinetic stabilization of microtubule dynamic instability by benomyl increases the nuclear transport of p53

“…It has been shown to have a very low acute systemic toxicity (LD 50 greater than 10 g/kg) in rats [3]. Tubulin is believed to be the target of benomyl in yeast cells based on specific mutation studies in the b tubulin gene, which altered the resistance or sensitivity of yeast cells to benomyl [4][5][6]. Benomyl was thought to bind at or near the colchicine binding site based on their structural similarities and the fact that several members of the benzimidazole group of compounds inhibit the binding of colchicine to tubulin both competitively and noncompetitively [6][7][8].…”