title: Molecular basis of rifampin resistance in Streptococcus pneumoniae.
abstract: 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 microg/ml. Clinical isolate 55, for which the MIC was 256 microg/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.
authors.affiliation: Pneumococcal Diseases Research Unit of the MRC, SAIMR, and the University of the Witwatersrand, Johannesburg, South Africa. thanup@hotmail.com
authors.forename: T
authors.initials: T
authors.lastname: Padayachee
authors.forename: K P
authors.initials: KP
authors.lastname: Klugman
mesh_terms: D000595:Amino Acid Sequence; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000032:analysis*; D004352:Drug Resistance, Microbial / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012293:Rifampin / Q000494:pharmacology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics; D014169:Transformation, Bacterial
chemical_list: D000904:Antibiotics, Antitubercular; D004269:DNA, Bacterial; D012293:Rifampin