Affiliation:
1. Division of Drug Resistance, Sloan-Kettering Institute for Cancer Research, and Sloan-Kettering Division, Cornell University Graduate School of Medical Sciences, New York, New York 10021
Abstract
Resistance to the antifolates methasquin and amethopterin has been studied in new strains of
Streptococcus faecium
var.
durans
. Two methasquin-resistant strains (SF/MQ, SF/MQ
T
) and an amethopterin-resistant strain (SF/AM) were selected independently from the wild-type
S. faecium
var.
durans
(SF/O). SF/MQ
T
is a thymine auxotroph. Total dihydrofolate reductase activity was elevated in each of the resistant strains. The greatest increase (36-fold) was observed in extracts of SF/AM. The methasquin-resistant strains, SF/MQ and SF/MQ
T
, had 29-fold and 8-fold, respectively, more dihydrofolate reductase activity than the parental strain. Total dihydrofolate reductase activity of SF/O was separable by gel filtration into two components: a folate reductase (11%) and a specific dihydrofolate reductase (89%). Folate reductase activity was associated with 88% of the total dihydrofolate reductase activity of SF/MQ
T
, with specific dihydrofolate reductase activity accounting for the remaining 12%. In SF/MQ and SF/AM, folate reductase activity was associated with 97% of the total dihydrofolate reductase activity. Studies of the inhibition by methasquin and amethopterin of partially purified folate reductase and specific dihydrofolate reductase of the mutant strains suggested that resistance was not accompanied by changes in the affinities of these enzymes for either antifolate.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
3 articles.
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