TY - JOUR
T1 - Characterization of a mutationally altered dihydropteroate synthase contributing to sulfathiazole resistance in Escherichia coli
AU - Vedantam, Gayatri
AU - Nichols, Brian P.
PY - 1998
Y1 - 1998
N2 - A series of Escherichia coli strains were selected for increasing resistance to sulfathiazole. Resistance occurred in seven increments, suggesting the accumulation of several mutations that contributed to overall sulfathiazole resistance. All of the resistant strains had a sulfathiazole- resistant dihydropteroate synthase with a Pro to Ser substitution at amino acid position 64. Overproduction of the wild-type enzyme did not result in sulfathiazole resistance, however overproduction of the mutant enzyme resulted in significant resistance. Conversely, overproduction of the wild- type enzyme in a sulfathiazole-resistant background resulted in a decrease in resistance. Although the specific activity of DHPS in crude extracts was not significantly different from the wild type, the amino acid substitution resulted in an enzyme with a tenfold increase in the Km for p-aminobenzoate, and a 100-fold increase in the Ki for sulfathiazole.
AB - A series of Escherichia coli strains were selected for increasing resistance to sulfathiazole. Resistance occurred in seven increments, suggesting the accumulation of several mutations that contributed to overall sulfathiazole resistance. All of the resistant strains had a sulfathiazole- resistant dihydropteroate synthase with a Pro to Ser substitution at amino acid position 64. Overproduction of the wild-type enzyme did not result in sulfathiazole resistance, however overproduction of the mutant enzyme resulted in significant resistance. Conversely, overproduction of the wild- type enzyme in a sulfathiazole-resistant background resulted in a decrease in resistance. Although the specific activity of DHPS in crude extracts was not significantly different from the wild type, the amino acid substitution resulted in an enzyme with a tenfold increase in the Km for p-aminobenzoate, and a 100-fold increase in the Ki for sulfathiazole.
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U2 - 10.1089/mdr.1998.4.91
DO - 10.1089/mdr.1998.4.91
M3 - Article
C2 - 9650994
AN - SCOPUS:0031800579
VL - 4
SP - 91
EP - 97
JO - Microbial Drug Resistance
JF - Microbial Drug Resistance
SN - 1076-6294
IS - 2
ER -