Extensive re-modelling of the transpeptidase domain of penicillin-binding protein 2B of a penicillin-resistant South African isolate of Streptococcus pneumoniae.
Clinical isolates of Streptococcus pneumoniae that have greatly increased levels of resistance to penicillin (greater than 1000-fold) have been reported from South Africa during the last ten years. Penicillin resistance in these strains is entirely due to the development of penicillin-binding proteins (PBPs) with decreased affinity for penicillin. We have cloned and sequenced the coding region for the transpeptidase domain of penicillin-binding protein 2B from three penicillin-sensitive strains of S. pneumoniae and from a penicillin-resistant South African strain. The amino acid sequences of the transpeptidase domains of PBP2B of the three penicillin-sensitive strains were identical and there were only between one and four differences in the nucleotide sequences of their coding regions. The corresponding region of the PBP2B gene from the penicillin-resistant strain differed by 74 nucleotide substitutions which resulted in 17 alterations in the amino acid sequence of PBP2B. The most remarkable alteration that has occurred during the development of the 'penicillin-resistant' form of PBP2B is the substitution of seven consecutive residues in a region that is predicted to form a loop at the bottom of the penicillin-binding site.
Dowson
C G
CG
School of Biological Sciences, University of Sussex, Brighton, UK.
Hutchison
A
A
Spratt
B G
BG
D000217:Acyltransferases / Q000235:genetics*; D000595:Amino Acid Sequence; D019881:Aminoacyltransferases; D001426:Bacterial Proteins; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D006602:Hexosyltransferases / Q000235:genetics*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D002267:Muramoylpentapeptide Carboxypeptidase; D010403:Penicillin Resistance / Q000235:genetics*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000235:genetics*; D011487:Protein Conformation; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000235:genetics*; D014169:Transformation, Bacterial
D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D000217:Acyltransferases; D019881:Aminoacyltransferases; C478701:penicillin-binding protein 2b, Streptococcus; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase