Recent Evolution of Susceptibility to Beta-Lactams in <i>Neisseria meningitidis</i>
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 acquisiti...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/12/6/992 |
| 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. |
|---|---|
| ISSN: | 2079-6382 |