title: Penicillin-binding proteins 2x and 2b as primary PBP targets in Streptococcus pneumoniae.
abstract: Different penicillin-binding proteins PBPs are affected in cefotaxime-resistant laboratory mutants compared to piperacillin-resistant mutants. PBP2x acts as the primary PBP target in cefotaxime-resistant mutants, whereas PBP2b is the primary target in piperacillin-resistant mutants. Depending on the mutations in PBP2x, it functions as a resistance determinant for cefotaxime only, or for penicillins as well. Mutations in PBP2x of laboratory mutants are found exclusively in the penicillin-binding domain that contains three homology boxes common to all penicillin-interacting enzymes. Most mutations relevant for resistance occur close to the SXN or the KT/SG box, or at the C-terminal end of the penicillin-binding domain, similar to mutations described in PBP2b of laboratory mutants. Amino acid alterations occur at similar sites also in PBP2x of beta-lactam-resistant clinical isolates and most of these proteins also contain changes in the SXXK box with the active site serine, suggesting that these alterations may be critical for resistance development in clinical isolates.
authors.affiliation: Max-Planck Institut für Molekulare Genetik, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Krauss
authors.forename: M
authors.initials: M
authors.lastname: van der Linden
authors.forename: T
authors.initials: T
authors.lastname: Grebe
authors.forename: R
authors.initials: R
authors.lastname: Hakenbeck
mesh_terms: D019881:Aminoacyltransferases; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000235:genetics*; D002439:Cefotaxime / Q000494:pharmacology; D018550:Cephalosporin Resistance; D002511:Cephalosporins / Q000494:pharmacology; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics*; D009154:Mutation; D010403:Penicillin Resistance / Q000235:genetics*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology; D010458:Peptidyl Transferases; D010878:Piperacillin / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000235:genetics*; D014169:Transformation, Bacterial
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D019881:Aminoacyltransferases; C478701:penicillin-binding protein 2b, Streptococcus; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D002439:Cefotaxime; D010878:Piperacillin