Over-production of dihydrofolate reductase leads to sulfa-dihydropteroate resistance in yeast

Onisha Patel, Kuldeep Karnik, Ian G Macreadie

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)301 - 305
Number of pages5
JournalFEMS Microbiology Letters
Volume236
Issue number2
DOIs
Publication statusPublished - 2004

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