Mutation frequency in antibiotic-resistant and -susceptible isolates of Streptococcus pneumoniae

Development of multiple antibiotic resistance in Streptococcus pneumoniae typically involves either mutation or transformation at several well-separated chromosomal loci. We postulated that this series of genetic events would be more likely to occur in organisms with deficient DNA repair mechanisms. Investigation of 27 antibiotic-resistant or -susceptible clinical isolates of S. pneumoniae revealed a broad range of mutation frequencies, but no isolate was as mutable as a mismatch repair (MMR)-deficient laboratory isolate. No correlation was observed between antibiotic resistance and higher mutation frequency. Examination of a further 180 clinical isolates using a newly developed rapid screen method also failed to identify any isolates with a mutation frequency as high as the MMR-deficient control strain. We argue that there is currently no clear evidence of a distinct population of mutators among clinical pneumococci.