Molecular evolution of rifampicin resistance in Streptococcus pneumoniae

Rifampicin resistance has arisen in several different species of bacteria b ecause of alterations to one or more regions in the target of the antibioti c, the beta-subunit of RNA polymerase encoded by rpoB, Nucleotide sequence analysis of a 270 bp fragment of rpoB from 16 clinical rifampicin-susceptib le isolates of Streptococcus pneumoniae, 8 clinical rifampicin-resistant is olates, and 3 spontaneous rifampicin-resistant mutants, has revealed that, as with previously examined species, point mutations within the cluster I r egion of rpoB, at sites encoding Asp(516) and His(526), also confer resista nce 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 a lter in resistant isolates of Escherichia coli and Mycobacterium tuberculos is. Sequence analysis of rpoB, both from these isolates of S. pneumoniae an d from two strains of S. mitis, reveals that, among a number of clinical is olates, resistance to rifampicin in S, pneumoniae has arisen by point mutat ion. However, the nucleotide sequence of rpoB from one isolate examined sug gests that interspecies gene transfer may also have played a role in the ev olution of rifampicin-resistance in S, pneumoniae.