CHARACTERIZATION OF MUTATIONS CONTRIBUTING TO SULFATHIAZOLE RESISTANCE IN ESCHERICHIA-COLI

A Sulfathiazole-resistant dihydropteroate synthase (DHPS) present in t wo different laboratory strains of Escherichia coli repeatedly selecte d for sulfathiazole resistance was mapped to folP by P1 transduction, The folP mutation in each of the strains was shown to be identical by nucleotide sequence analysis, A single C-->T transition resulted in a Pro-->Ser substitution at amino acid position 64. Replacement of the m utant folP alleles with wild-type folP significantly reduced the level of resistance to sulfathiazole but did not abolish it, indicating the presence of an additional mutation(s) that contributes to sulfathiazo le resistance in the two strains, Transfer of the mutant folP allele t o a wild-type background resulted in a strain with only a low level of resistance to sulfathiazole, suggesting that the presence of the resi stant DHPS was not in itself sufficient to account for the overall sul fathiazole resistance in these strains of E. coli. Additional characte rization of an amplified secondary resistance determinant, sur, presen t in one of the strains, identified it as the previously identified bi cyclomycin resistance determinant bcr, a member of a family of membran e-bound multidrug resistance antiporters, An additional mutation contr ibuting to sulfathiazole resistance, sux, has also been identified and has been shown to affect the histidine response to adenine sensitivit y displayed by these purU strains.