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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...

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Autores principales: Deghmane, Ala-Eddine, Hong, Eva, Taha, Muhamed-Kheir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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