title: Molecular evolution of rifampicin resistance in Streptococcus pneumoniae.
abstract: Rifampicin resistance has arisen in several different species of bacteria because of alterations to one or more regions in the target of the antibiotic, the beta-subunit of RNA polymerase encoded by rpoB. Nucleotide sequence analysis of a 270 bp fragment of rpoB from 16 clinical rifampicin-susceptible isolates of Streptococcus pneumoniae, 8 clinical rifampicin-resistant isolates, and 3 spontaneous rifampicin-resistant mutants, has revealed that, as with previously examined species, point mutations within the cluster I region of rpoB, at sites encoding Asp516 and HiS526, also confer resistance to rifampicin in this important human pathogen. Moreover, the residues within cluster I, that were altered within the rifampicin-resistant mutants of S. pneumoniae, were in the same position as those previously found to alter in resistant isolates of Escherichia coli and Mycobacterium tuberculosis. Sequence analysis of rpoB, both from these isolates of S. pneumoniae and from two strains of S. mitis, reveals that, among a number of clinical isolates, resistance to rifampicin in S. pneumoniae has arisen by point mutation. However, the nucleotide sequence of rpoB from one isolate examined suggests that interspecies gene transfer may also have played a role in the evolution of rifampicin-resistance in S. pneumoniae.
authors.affiliation: Department of Biochemistry, University of Sussex, Brighton, UK.
authors.forename: M
authors.initials: M
authors.lastname: Enright
authors.forename: P
authors.initials: P
authors.lastname: Zawadski
authors.forename: P
authors.initials: P
authors.lastname: Pickerill
authors.forename: C G
authors.initials: CG
authors.lastname: Dowson
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000235:genetics*; D004352:Drug Resistance, Microbial; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012293:Rifampin / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D014169:Transformation, Bacterial
chemical_list: D000900:Anti-Bacterial Agents; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin