Recent Evolution of Susceptibility to Beta-Lactams in <i>Neisseria meningitidis</i>

• Main Authors: Ala-Eddine Deghmane (Author), Eva Hong (Author), Muhamed-Kheir Taha (Author)
• Format: Book
• Published: MDPI AG, 2023-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Beta-lactams are the main antibiotics for the treatment of invasive meningococcal disease. However, reduced susceptibility to penicillin G is increasingly reported in <i>Neisseria meningitidis</i> and reduced susceptibility to third-generation cephalosporines (3GC) and the rare acquisition of ROB-1 beta-lactamase were also described. Modifications of penicillin-binding protein 2 (PBP2) encoded by the <i>penA</i> gene are the main described mechanism for the reduced susceptibility to penicillin and to other beta-lactams. <i>penA</i> modifications were analyzed using the sequences of all <i>penA</i> genes from cultured isolates between 2017-2021 in France (<i>n</i> = 1255). Data showed an increasing trend of reduced susceptibility to penicillin from 36% in 2017 to 58% in 2021. Reduced susceptibility to 3GC remained limited at 2.4%. We identified 74 different <i>penA</i> alleles and <i>penA1</i> was the most frequent wild-type allele and represented 29% of all alleles while <i>penA9</i> was the most frequently altered allele and represented 17% of all alleles. Reduced susceptibility to 3GC was associated with the <i>penA327</i> allele. The amino acid sequences of wild-type and altered PBP2 were modeled. The critical amino acid substitutions were shown to change access to the active S310 residue and hence hinder the binding of beta-lactams to the active site of PBP2.

Item Description

10.3390/antibiotics12060992
2079-6382