title: Over-production of dihydrofolate reductase leads to sulfa-dihydropteroate resistance in yeast.
abstract: Dihydropteroate synthase (DHPS) can metabolise sulfa drugs into sulfa-dihydropteroate (sulfa-DHP), which inhibits cell growth through competition with dihydrofolate (DHF), possibly indicating dihydrofolate reductase (DHFR) as the target of sulfa-DHP. The effect of over-production of DHFR on sulfa-DHP resistance was examined in Saccharomyces cerevisiae using a strain that requires DHF for growth. This strain was transformed with a plasmid which encodes over-production of DHFR in the presence of CuSO4. Over-production led to resistance to sulfa-DHP suggesting that sulfa-DHP targets DHFR. Spontaneous mutants hyper-resistant to sulfa-DHP did not show any changes within DHFR.
authors.affiliation: CSIRO Health Sciences and Nutrition, Parkville, Vic., Australia.
authors.forename: Onisha
authors.initials: O
authors.lastname: Patel
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Karnik
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macreadie
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development / Q000378:metabolism; D013420:Sulfamethoxazole / Q000494:pharmacology*; D000077589:Sulfathiazole; D013432:Sulfathiazoles / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D000890:Anti-Infective Agents; D013432:Sulfathiazoles; D013762:Tetrahydrofolate Dehydrogenase; D013420:Sulfamethoxazole; D000077589:Sulfathiazole