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

Onisha Patel; Kuldeep Karnik; Ian G Macreadie

doi:10.1111/j.1574-6968.2004.tb09661.x

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

Onisha Patel, Kuldeep Karnik, Ian G Macreadie

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › Research › peer-review

6 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 language	English
Pages (from-to)	301 - 305
Number of pages	5
Journal	FEMS Microbiology Letters
Volume	236
Issue number	2
DOIs	https://doi.org/10.1111/j.1574-6968.2004.tb09661.x
Publication status	Published - 2004

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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.",

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AU - Patel, Onisha

AU - Karnik, Kuldeep

AU - Macreadie, Ian G

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N2 - 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.

AB - 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.

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DO - 10.1111/j.1574-6968.2004.tb09661.x

M3 - Article

VL - 236

SP - 301

EP - 305

JO - FEMS Microbiology Letters

JF - FEMS Microbiology Letters

SN - 0378-1097

IS - 2

ER -

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

Abstract

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