Horizontal Transfer of Penicillin-Binding Protein Genes in Penicillin-Resistant Clinical Isolates of Streptococcus pneumoniae

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-11, Vol.86 (22), p.8842-8846
• Main Authors: Dowson, Christopher G., Hutchison, Agnes, Brannigan, James A., George, Robert C., Hansman, David, Liñares, Josefina, Tomasz, Alex, Smith, John Maynard, Spratt, Brian G.
• Format: Article
• Language: English
• Subjects: Amino acids; Aminoacyltransferases; Bacterial Proteins; Bacteriology; Base Sequence; Biological and medical sciences; Carrier Proteins - genetics; Codons; Evolution; Evolutionary genetics; Fundamental and applied biological sciences. Psychology; Genes; Genes, Bacterial; Genetic Variation; Genetics; Hexosyltransferases; Humans; Microbiology; Molecular Sequence Data; Muramoylpentapeptide Carboxypeptidase - genetics; Nucleotides; Oligonucleotide Probes; Penicillin; Penicillin Resistance - genetics; Penicillin-Binding Proteins; Peptidyl Transferases; Sequence Homology, Nucleic Acid; Sequencing; Serotyping; Species Specificity; Streptococcus pneumoniae; Streptococcus pneumoniae - classification; Streptococcus pneumoniae - genetics; Streptococcus pneumoniae - isolation & purification; Transformation, Bacterial
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.22.8842

Resistance to penicillin in clinical isolates of Streptococcus pneumoniae has occurred by the development of altered penicillin-binding proteins (PBPs) that have greatly decreased affinity for the antibiotic. We have investigated the origins of penicillin-resistant strains by comparing the sequences of the transpeptidase domain of PBP2B from 6 penicillin-sensitive and 14 penicillin-resistant strains. In addition we have sequenced part of the amylomaltase gene from 2 of the sensitive and 6 of the resistant strains. The sequences of the amylomaltase gene of all of the strains and of the PBP2B gene of the penicillin-sensitive strains show that S. pneumoniae is genetically very uniform. In contrast the PBP2B genes of the penicillin-resistant strains show ≈ 14% sequence divergence from those of the penicillin-sensitive strains and the development of penicillin resistance has involved the replacement, presumably by transformation, of the original PBP2B gene by a homologous gene from an unknown source. This genetic event has occurred on at least two occasions, involving different sources, to produce the two classes of altered PBP2B genes found in penicillin-resistant strains of S. pneumoniae. There is considerable variation among the PBP2B genes of the resistant strains that may have arisen by secondary transformation events accompanied by mismatch repair subsequent to their original introductions into S. pneumoniae.