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Antimicrobial Agents and Chemotherapy, September 1999, p. 2225-2230, Vol. 43, No. 9
Pneumococcal Diseases Research Unit of the
Medical Research Council, The South African Institute for Medical
Research and the University of the Witwatersrand, Johannesburg, South
Africa
Received 28 April 1999/Returned for modification 8 June
1999/Accepted 14 July 1999
A study of eight sulfonamide-resistant clinical isolates of
Streptococcus pneumoniae revealed chromosomal mutations
within the gene encoding dihydropteroate synthase that play a role in conferring resistance to sulfamethoxazole. The presence of the suld mutation, found previously only in a laboratory
mutant, was shown to occur in three of the wild-type clinical isolates.
The duplication of Ser61, the other previously defined
mutation in the dihydropteroate synthase gene of S. pneumoniae, was observed in only one of the isolates
characterized. We report two previously unidentified amino acid
alterations, namely, a duplication of Arg58 and
Pro59 and an insertion of an arginine residue between Gly60 and Ser61 in
trimethoprim-sulfamethoxazole-resistant strains. The significance of
these mutations was confirmed by site-directed mutagenesis and by the
transformation of a susceptible strain of S. pneumoniae to
sulfamethoxazole resistance. Two resistant isolates did not contain any
mutations within the gene encoding dihydropteroate synthase. The
results presented suggest the independent generation of resistant
mutations among South African clinical isolates. It is also proposed
that the mechanism of sulfonamide resistance in S. pneumoniae involves the expansion of a specific region within
dihydropteroate synthase, which probably forms part of the sulfonamide
binding site.
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Novel Expansions of the Gene Encoding
Dihydropteroate Synthase in Trimethoprim-Sulfamethoxazole-Resistant
Streptococcus pneumoniae
*
Corresponding author. Present address: Department of
Clinical Microbiology and Infectious Diseases, SAIMR, P.O. Box 1038, Johannesburg 2000, South Africa. Phone: 27-11-4899335. Fax:
27-11-4899332. E-mail: thanup{at}hotmail.com.
Antimicrobial Agents and Chemotherapy, September 1999, p. 2225-2230, Vol. 43, No. 9
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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