ABSTRACTStreptococcus pneumoniaeis a leading cause of pneumonia, meningitis, septicemia, and middle ear infections. The incidence ofS. pneumoniaeisolates that are not susceptible to penicillin has risen worldwide and may be above 20% in some countries. Beta-lactam antibiotic resistance in pneumococci is associated with significant sequence polymorphism in penicillin-binding proteins (PBPs). Commensal streptococci, especiallyS. mitisandS. oralis, have been identified as putative donors of mutated gene fragments. However, no studies have compared sequences of the involvedpbpgenes in large collections of commensal streptococci with those ofS. pneumoniae. We therefore investigated the sequence diversity of the transpeptidase region of the threepbpgenes,pbp2x,pbp2b, andpbp1ain 107, 96, and 88 susceptible and nonsusceptible strains of commensal streptococci, respectively, at the nucleotide and amino acid levels to determine to what extent homologous recombination between commensal streptococci andS. pneumoniaeplays a role in the development of beta-lactam resistance inS. pneumoniae. In contrast to pneumococci, extensive sequence variation in the transpeptidase region ofpbp2x,pbp2b, andpbp1awas observed in both susceptible and nonsusceptible strains of commensal streptococci, conceivably reflecting the genetic diversity of the many evolutionary lineages of commensal streptococci combined with the recombination events occurring with intra- and interspecies homologues. Our data support the notion that resistance to beta-lactam antibiotics in pneumococci is due to sequences acquired from commensal Mitis group streptococci, especiallyS. mitis. However, several amino acid alterations previously linked to beta-lactam resistance in pneumococci appear to represent species signatures of the donor strain rather than being causal of resistance.
Lack of correlation between in vitro and in vivo studies of combinations of rifampin plus vancomycin or beta-lactam antibiotics against Streptococcus pneumoniae.
