title: Evolution of penicillin resistance in Streptococcus pneumoniae; the role of Streptococcus mitis in the formation of a low affinity PBP2B in S. pneumoniae.
abstract: Penicillin-resistant strains of Streptococcus pneumoniae possess forms of penicillin-binding proteins (PBPs) that have a low affinity for penicillin compared to those from penicillin-sensitive strains. PBP genes from penicillin-resistant isolates are very variable and have a mosaic structure composed of blocks of nucleotides that are similar to those found in PBP genes from penicillin-sensitive isolates and blocks that differ by up to 21%. These chromosomally encoded mosaic genes have presumably arisen following transformation and homologous recombination with PBP genes from a number of closely related species. This study shows that PBP2B genes from many penicillin-resistant isolates of S. pneumoniae contain blocks of nucleotides originating from Streptococcus mitis. In several instances it would appear that this material alone is sufficient to produce a low affinity PBP2B. In other examples PBP2B genes possess blocks of nucleotides from S. mitis and at least one additional unidentified species. Mosaic structure was also found in the PBP2B genes of penicillin-sensitive isolates of S. mitis or S. pneumoniae. These mosaics did not confer penicillin resistance but nevertheless reveal something of the extent to which localized recombination occurs in these naturally transformable streptococci.
authors.affiliation: Microbial Genetics Group, School of Biological Sciences, University of Sussex, Falmer, Brighton, UK.
authors.forename: C G
authors.initials: CG
authors.lastname: Dowson
authors.forename: T J
authors.initials: TJ
authors.lastname: Coffey
authors.forename: C
authors.initials: C
authors.lastname: Kell
authors.forename: R A
authors.initials: RA
authors.lastname: Whiley
mesh_terms: D000595:Amino Acid Sequence; D019881:Aminoacyltransferases; D001426:Bacterial Proteins; D001483:Base Sequence; D005075:Biological Evolution; D002352:Carrier Proteins; D005798:Genes, Bacterial / Q000235:genetics; D014644:Genetic Variation; D006602:Hexosyltransferases / Q000145:classification / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000145:classification / Q000235:genetics*; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G / Q000494:pharmacology; D010403:Penicillin Resistance / Q000235:genetics*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000145:classification / Q000235:genetics*; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013291:Streptococcus / Q000187:drug effects / Q000235:genetics*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics*; D014170:Transformation, Genetic
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D019881:Aminoacyltransferases; C478701:penicillin-binding protein 2b, Streptococcus; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G