Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis

Area of Science:

• Microbiology
• Genetics
• Pharmacology

Background:

• Beta-lactam antibiotics are crucial for treating invasive meningococcal disease.
• Increasing resistance to penicillin G in Neisseria meningitidis is a growing concern.
• Reduced susceptibility to third-generation cephalosporines (3GC) and the presence of ROB-1 beta-lactamase have also been noted.

Purpose of the Study:

• To analyze modifications in the penA gene, which encodes penicillin-binding protein 2 (PBP2), in Neisseria meningitidis isolates in France.
• To track trends in beta-lactam antibiotic susceptibility in N. meningitidis from 2017 to 2021.
• To investigate the molecular mechanisms underlying reduced susceptibility.

Main Methods:

• Sequencing of all penA genes from 1255 N. meningitidis isolates cultured between 2017 and 2021.
• Analysis of trends in reduced susceptibility to penicillin and 3GC.
• Identification and characterization of penA alleles.
• Molecular modeling of wild-type and altered PBP2 amino acid sequences.

Main Results:

• Reduced susceptibility to penicillin increased from 36% in 2017 to 58% in 2021.
• Reduced susceptibility to 3GC remained low at 2.4%.
• 74 different penA alleles were identified; penA9 was the most frequent altered allele (17%).
• The penA327 allele was associated with reduced 3GC susceptibility.
• Amino acid substitutions in PBP2 were shown to hinder beta-lactam binding.

Conclusions:

• PenA modifications are the primary mechanism for beta-lactam resistance in N. meningitidis.
• The increasing prevalence of specific penA alleles correlates with rising penicillin resistance.
• Understanding these genetic changes is vital for guiding antibiotic treatment strategies.