This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Swedberg, G.
Right arrow Articles by Sköld, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Swedberg, G.
Right arrow Articles by Sköld, O.

 Previous Article  |  Next Article 

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.



This article has been cited by other articles:

  • Giordanetto, F., Fowler, P. W, Saqi, M., Coveney, P. V (2005). Large scale molecular dynamics simulation of native and mutant dihydropteroate synthase-sulphanilamide complexes suggests the molecular basis for dihydropteroate synthase drug resistance. Phil Trans R Soc A 363: 2055-2073 [Abstract] [Full Text]  
  • Iliades, P., Meshnick, S. R., Macreadie, I. G. (2004). Dihydropteroate Synthase Mutations in Pneumocystis jiroveci Can Affect Sulfamethoxazole Resistance in a Saccharomyces cerevisiae Model. Antimicrob. Agents Chemother. 48: 2617-2623 [Abstract] [Full Text]  
  • Zingale, A., Carrera, P., Lazzarin, A., Scarpellini, P. (2003). Detection of Pneumocystis carinii and Characterization of Mutations Associated with Sulfa Resistance in Bronchoalveolar Lavage Samples from Human Immunodeficiency Virus-Infected Subjects. J. Clin. Microbiol. 41: 2709-2712 [Abstract] [Full Text]  
  • Williams, D. L., Pittman, T. L., Gillis, T. P., Matsuoka, M., Kashiwabara, Y. (2001). Simultaneous Detection of Mycobacterium leprae and Its Susceptibility to Dapsone Using DNA Heteroduplex Analysis. J. Clin. Microbiol. 39: 2083-2088 [Abstract] [Full Text]  
  • Haasum, Y., Ström, K., Wehelie, R., Luna, V., Roberts, M. C., Maskell, J. P., Hall, L. M. C., Swedberg, G. (2001). Amino Acid Repetitions in the Dihydropteroate Synthase of Streptococcus pneumoniae Lead to Sulfonamide Resistance with Limited Effects on Substrate Km. Antimicrob. Agents Chemother. 45: 805-809 [Abstract] [Full Text]  
  • Doherty, N., Trzcinski, K., Pickerill, P., Zawadzki, P., Dowson, C. G. (2000). Genetic Diversity of the tet(M) Gene in Tetracycline-Resistant Clonal Lineages of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 44: 2979-2984 [Abstract] [Full Text]  
  • Williams, D. L., Spring, L., Harris, E., Roche, P., Gillis, T. P. (2000). Dihydropteroate Synthase of Mycobacterium leprae and Dapsone Resistance. Antimicrob. Agents Chemother. 44: 1530-1537 [Abstract] [Full Text]  
  • Gibreel, A., Sköld, O. (1999). Sulfonamide Resistance in Clinical Isolates of Campylobacter jejuni: Mutational Changes in the Chromosomal Dihydropteroate Synthase. Antimicrob. Agents Chemother. 43: 2156-2160 [Abstract] [Full Text]