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Antimicrobial Agents and Chemotherapy, October 1999, p. 2361-2365, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Molecular Basis of Rifampin Resistance in Streptococcus pneumoniae

Thanugarani Padayachee* and Keith P. Klugman

Pneumococcal Diseases Research Unit of the MRC, SAIMR, and the University of the Witwatersrand, Johannesburg, South Africa

Received 26 February 1999/Returned for modification 2 June 1999/Accepted 27 July 1999

Rifampin resistance among South African clinical isolates of Streptococcus pneumoniae was shown to be due to missense mutations within the rpoB gene. Sequence analysis of 24 rifampin-resistant isolates revealed the presence of mutations within cluster I as well as novel mutations in an area designated pneumococcus cluster III. Of the 24 isolates characterized, only 1 resistant isolate did not contain any mutations in the regions sequenced. Either the cluster I or the cluster III mutations separately conferred MICs of 32 to 128 µg/ml. Clinical isolate 55, for which the MIC was 256 µg/ml, was noted to contain 9 of the 10 mutations identified, which included the cluster I and cluster III mutations. As in Escherichia coli, it is possible that cluster I (amino acids 406 to 434) and cluster III (amino acids 523 to 600) of S. pneumoniae interact to form part of the antibiotic binding site, thus accounting for the very high MIC observed for isolate 55. PCR products containing cluster I or cluster III mutations were able to transform rifampin-susceptible S. pneumoniae to resistance. Although many of the isolates studied displayed identical sequences, pulsed-field gel electrophoresis analysis revealed that the isolates were not of clonal origin.

* Corresponding author. Mailing 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, October 1999, p. 2361-2365, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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