Folic acid utilisation related to sulfa drug resistance in Saccharomyces cerevisiae

被引:22
作者
Bayly, AM
Berglez, JM
Patel, O
Castelli, LA
Hankins, EG
Coloe, P
Sibley, CH
Macreadie, IG
机构
[1] CSIRO, Hlth & Sci Nutr, Parkville, Vic, Australia
[2] Univ Bundoora, RMIT, Bundoora, Vic, Australia
[3] Univ Washington, Dept Genet, Seattle, WA 98195 USA
关键词
antifolate; dihydrofolic acid; dihydropteroic acid; folate salvage; folinic acid; Plasmodium falciparum; sulfa drug;
D O I
10.1111/j.1574-6968.2001.tb10915.x
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Saccharomyces cervisiae mutants deficient in folate synthesis have been constructed and employed to study the utilisation of exogenous folates in yeast. One mutant specifically lacked dihydropteroate synthase while the second lacked dihydrofolate synthase. Exogenous folinic acid restored optimal growth to both strains. Folic acid did not generally rescue growth but spontaneous isolates capable of utilising folic acid were selected. The folic acid synthesis pathway in the folate utilising isolates was restored via transformation with FOL1 or FOL3 expression plasmids and transformants were tested for resistance to sulfamethoxazole (SMX). The presence of elevated levels of folic acid led to greatly reduced SMX sensitivity regardless of whether strains were folate utilisers or not. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:387 / 390
页数:4
相关论文
共 8 条
[1]   Sulfa drug screening in yeast:: fifteen sulfa drugs compete with p-aminobenzoate in Saccharomyces cerevisiae [J].
Castelli, LA ;
Nguyen, NP ;
Macreadie, IG .
FEMS MICROBIOLOGY LETTERS, 2001, 199 (02) :181-184
[2]   IMPROVED METHOD FOR HIGH-EFFICIENCY TRANSFORMATION OF INTACT YEAST-CELLS [J].
GIETZ, D ;
STJEAN, A ;
WOODS, RA ;
SCHIESTL, RH .
NUCLEIC ACIDS RESEARCH, 1992, 20 (06) :1425-1425
[3]   THE PHENOTYPE OF A DIHYDROFOLATE-REDUCTASE MUTANT OF SACCHAROMYCES-CEREVISIAE [J].
HUANG, T ;
BARCLAY, BJ ;
KALMAN, TI ;
VONBORSTEL, RC ;
HASTINGS, PJ .
GENE, 1992, 121 (01) :167-171
[4]   YEAST VECTORS FOR THE CONTROLLED EXPRESSION OF HETEROLOGOUS PROTEINS IN DIFFERENT GENETIC BACKGROUNDS [J].
MUMBERG, D ;
MULLER, R ;
FUNK, M .
GENE, 1995, 156 (01) :119-122
[5]   Selection and synergy in Plasmodium falciparum [J].
Sims, P ;
Wang, P ;
Hyde, JE .
PARASITOLOGY TODAY, 1999, 15 (04) :132-134
[6]   On 'the efficacy of antifolate antimalarial combinations in Africa' [J].
Sims, P ;
Wang, P ;
Hyde, JE .
PARASITOLOGY TODAY, 1998, 14 (04) :136-137
[7]   Sulfadoxine resistance in the human malaria parasite Plasmodium falciparum is determined by mutations in dihydropteroate synthetase and an additional factor associated with folate utilization [J].
Wang, P ;
Read, M ;
Sims, PFG ;
Hyde, JE .
MOLECULAR MICROBIOLOGY, 1997, 23 (05) :979-986
[8]   More on 'the efficacy of antifolate antimalarial combinations in Africa' [J].
Watkins, WM ;
Mberu, EK ;
Winstanley, PA ;
Plowe, CV .
PARASITOLOGY TODAY, 1999, 15 (04) :131-132