PENICILLIN-BINDING PROTEINS 2X AND 2B AS PRIMARY PBP TARGETS IN STREPTOCOCCUS-PNEUMONIAE

Different penicillin-binding proteins PBPs are affected in cefotaxime- resistant laboratory mutants compared to piperacillin-resistant mutant s. PBP2x acts as the primary PBP target in cefotaxime-resistant mutant s, whereas PBP2b is the primary target in piperacillin-resistant mutan ts. 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 penicilli n-binding domain that contains three homology boxes common to all peni cillin-interacting enzymes. Most mutations relevant for resistance occ ur 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 se rine, suggesting that these alterations may be critical for resistance development in clinical isolates.