Correlation between alterations of the penicillin-binding protein 2 and modifications of the peptidoglycan structure in Neisseria meningitidis with reduced susceptibility to penicillin G.
Reduced susceptibility to penicillin G in Neisseria meningitidis is directly correlated with alterations in the penA gene, which encodes the penicillin-binding protein 2 (PBP2). Using purified PBP2s from different backgrounds, we confirmed that the reduced susceptibility to penicillin G is associated with a decreased affinity of altered PBP2s for penicillin G. Infrared spectroscopy analysis using isogenic penicillin-susceptible strains and strains with reduced susceptibility to penicillin G suggested that the meningococcal cell wall is also modified in a penA-dependent manner. Moreover, reverse-phase high pressure liquid chromatography and mass spectrometry analysis of these meningococcal strains confirmed the modifications of peptidoglycan components and showed an increase in the peaks corresponding to pentapeptide-containing muropeptides. These results suggest that the D,D-transpeptidase and/or D,D-carboxypeptidase activities of PBP2 are modified by the changes in penA gene.
Antignac
Aude
A
Unité des Neisseria and Centre National de Référence des Méningocoques, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
Boneca
Ivo G
IG
Rousselle
Jean-Claude
JC
Namane
Abdelkader
A
Carlier
Jean-Philippe
JP
Vázquez
Julio A
JA
Fox
Andrew
A
Alonso
Jean-Michel
JM
Taha
Muhamed-Kheir
MK
D002851:Chromatography, High Pressure Liquid; D008826:Microbial Sensitivity Tests; D009345:Neisseria meningitidis / Q000737:chemistry* / Q000187:drug effects; D010400:Penicillin G / Q000494:pharmacology*; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared
D010400:Penicillin G