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Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis
Beta-lactams are the main antibiotics for the treatment of invasive meningococcal disease. However, reduced susceptibility to penicillin G is increasingly reported in Neisseria meningitidis and reduced susceptibility to third-generation cephalosporines (3GC) and the rare acquisition of ROB-1 beta-la...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295462/ https://www.ncbi.nlm.nih.gov/pubmed/37370311 http://dx.doi.org/10.3390/antibiotics12060992 |
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author | Deghmane, Ala-Eddine Hong, Eva Taha, Muhamed-Kheir |
author_facet | Deghmane, Ala-Eddine Hong, Eva Taha, Muhamed-Kheir |
author_sort | Deghmane, Ala-Eddine |
collection | PubMed |
description | Beta-lactams are the main antibiotics for the treatment of invasive meningococcal disease. However, reduced susceptibility to penicillin G is increasingly reported in Neisseria meningitidis 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 penA gene are the main described mechanism for the reduced susceptibility to penicillin and to other beta-lactams. penA modifications were analyzed using the sequences of all penA genes from cultured isolates between 2017–2021 in France (n = 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 penA alleles and penA1 was the most frequent wild-type allele and represented 29% of all alleles while penA9 was the most frequently altered allele and represented 17% of all alleles. Reduced susceptibility to 3GC was associated with the penA327 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. |
format | Online Article Text |
id | pubmed-10295462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102954622023-06-28 Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis Deghmane, Ala-Eddine Hong, Eva Taha, Muhamed-Kheir Antibiotics (Basel) Article Beta-lactams are the main antibiotics for the treatment of invasive meningococcal disease. However, reduced susceptibility to penicillin G is increasingly reported in Neisseria meningitidis 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 penA gene are the main described mechanism for the reduced susceptibility to penicillin and to other beta-lactams. penA modifications were analyzed using the sequences of all penA genes from cultured isolates between 2017–2021 in France (n = 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 penA alleles and penA1 was the most frequent wild-type allele and represented 29% of all alleles while penA9 was the most frequently altered allele and represented 17% of all alleles. Reduced susceptibility to 3GC was associated with the penA327 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. MDPI 2023-06-01 /pmc/articles/PMC10295462/ /pubmed/37370311 http://dx.doi.org/10.3390/antibiotics12060992 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Deghmane, Ala-Eddine Hong, Eva Taha, Muhamed-Kheir Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis |
title | Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis |
title_full | Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis |
title_fullStr | Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis |
title_full_unstemmed | Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis |
title_short | Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis |
title_sort | recent evolution of susceptibility to beta-lactams in neisseria meningitidis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295462/ https://www.ncbi.nlm.nih.gov/pubmed/37370311 http://dx.doi.org/10.3390/antibiotics12060992 |
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