G. Vedantam et Bp. Nichols, CHARACTERIZATION OF A MUTATIONALLY ALTERED DIHYDROPTEROATE SYNTHASE CONTRIBUTING TO SULFATHIAZOLE RESISTANCE IN ESCHERICHIA-COLI, Microbial drug resistance, 4(2), 1998, pp. 91-97
A series of Escherichia coli strains were selected for increasing resi
stance to sulfathiazole. Resistance occurred in seven increments, sugg
esting the accumulation of several mutations that contributed to overa
ll sulfathiazole resistance, All of the resistant strains had a sulfat
hiazote-resistant dihydropteroate synthase with a Pro to Ser substitut
ion 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, over
production of the wild-type enzyme in a sulfathiazole-resistant backgr
ound resulted in a decrease in resistance, Although the specific activ
ity of DHPS in crude extracts was not significantly different from the
wild type, the amino acid substitution resulted in an enzyme with a t
enfold increase in the Km for p-aminobenzoate, and a 100-fold increase
in the Ri for sulfathiazole.