Over-production of dihydrofolate reductase leads to sulfa-dihydropteroate resistance in yeast.
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.
Patel
Onisha
O
CSIRO Health Sciences and Nutrition, Parkville, Vic., Australia.
Karnik
Kuldeep
K
Macreadie
Ian G
IG
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*
D000890:Anti-Infective Agents; D013432:Sulfathiazoles; D013762:Tetrahydrofolate Dehydrogenase; D013420:Sulfamethoxazole; D000077589:Sulfathiazole