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Antimicrobial Agents and Chemotherapy, May 1998, p. 1062-1067, Vol. 42, No. 5
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Sulfonamide Resistance in Streptococcus pyogenes Is Associated with Differences in the Amino Acid Sequence of Its Chromosomal Dihydropteroate Synthase

Göte Swedberg,1,* Signe Ringertz,2,dagger and Ola Sköld1

Department of Pharmaceutical Biosciences, Division of Microbiology, Biomedical Centre, Uppsala University, Uppsala,1 and Department of Clinical Microbiology, Karolinska Hospital, Solna,2 Sweden

Received 2 September 1997/Returned for modification 29 October 1997/Accepted 25 February 1998

Sulfonamide resistance in recent isolates of Streptococcus pyogenes was found to be associated with alterations of the chromosomally encoded dihydropteroate synthase (DHPS). There were 111 different nucleotides (13.8%) in the genes found in susceptible and resistant isolates, respectively, resulting in 30 amino acid changes (11.3%). These substantial changes suggested the possibility of a foreign origin of the resistance gene, in parallel to what has already been found for sulfonamide resistance in Neisseria meningitidis. The gene encoding DHPS was linked to at least three other genes encoding enzymes of the folate pathway. These genes were in the order GTP cyclohydrolase, dihydropteroate synthase, dihydroneopterin aldolase, and hydroxymethyldihydropterin pyrophosphokinase. The nucleotide differences in genes from resistant and susceptible strains extended from the beginning of the GTP cyclohydrolase gene to the end of the gene encoding DHPS, an additional indication for gene transfer in the development of resistance. Kinetic measurements established different affinities for sulfathiazole for DHPS enzymes isolated from resistant and susceptible strains.

* Corresponding author. Mailing address: Department of Pharmaceutical Biosciences, Division of Microbiology, Biomedical Centre, Box 581, S-751 23 Uppsala, Sweden. Phone: 46-18-471 46 19. Fax: 46-18-502790. E-mail: gote.swedberg{at}farmbio.uu.se.

dagger Present address: Bakteriologisk Laboratorium, Aker Sykehus, Oslo, Norway.

Antimicrobial Agents and Chemotherapy, May 1998, p. 1062-1067, Vol. 42, No. 5
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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