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Antimicrobial Agents and Chemotherapy, January 1998, p. 88-93, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Characterization of Mutations Contributing to Sulfathiazole Resistance in Escherichia coli

Gayatri Vedantam,dagger Gordon G. Guay,Dagger Natasha E. Austria, Stella Z. Doktor,§ and Brian P. Nichols*

Laboratory for Molecular Biology, Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607

Received 22 May 1997/Returned for modification 7 August 1997/Accepted 28 October 1997

A sulfathiazole-resistant dihydropteroate synthase (DHPS) present in two different laboratory strains of Escherichia coli repeatedly selected 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 Cright-arrowT transition resulted in a Proright-arrowSer substitution at amino acid position 64. Replacement of the mutant 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 sulfathiazole resistance in the two strains. Transfer of the mutant folP allele to a wild-type background resulted in a strain with only a low level of resistance to sulfathiazole, suggesting that the presence of the resistant DHPS was not in itself sufficient to account for the overall sulfathiazole resistance in these strains of E. coli. Additional characterization of an amplified secondary resistance determinant, sur, present in one of the strains, identified it as the previously identified bicyclomycin resistance determinant bcr, a member of a family of membrane-bound multidrug resistance antiporters. An additional mutation contributing to sulfathiazole resistance, sux, has also been identified and has been shown to affect the histidine response to adenine sensitivity displayed by these purU strains.

* Corresponding author. Mailing address: Laboratory for Molecular Biology, Department of Biological Sciences, Molecular Biology Research Building m/c 567, University of Illinois at Chicago, 900 S. Ashland Ave., Chicago, IL 60607. Phone: (312) 996-5064. Fax: (312) 413-2691. E-mail: brian.p.nichols{at}uic.edu.

dagger Present address: Department of Microbiology, Strich School of Medicine, Loyola University of Chicago, Maywood, IL 60153.

Dagger Present address: Gillette Company, Boston, MA 02127.

§ Present address: Department of Cellular, Molecular and Structural Biology, Northwestern University Medical School, Chicago, IL 60611.

Antimicrobial Agents and Chemotherapy, January 1998, p. 88-93, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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