PBP2a in β-Lactam-Resistant Laboratory Mutants and Clinical Isolates: Disruption Versus Reduced Penicillin Affinity

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• Penicillin-binding protein 2a (PBP2a) alterations are linked to cefotaxime resistance in laboratory mutants and beta-lactam resistance in clinical isolates of Streptococcus pneumoniae.
• Understanding the genetic basis of these alterations is crucial for combating antibiotic resistance.

Purpose of the Study:

• To investigate the distinct genetic mechanisms underlying PBP2a alterations in laboratory-generated cefotaxime-resistant Streptococcus pneumoniae mutants compared to clinical beta-lactam-resistant isolates.
• To identify the source of resistance determinants in clinical strains.

Main Methods:

• DNA sequencing of the pbp2a gene in laboratory mutants and clinical isolates of Streptococcus pneumoniae.
• Comparative sequence analysis to identify mutations, duplications, and mosaic gene structures.

Main Results:

• Laboratory mutants exhibited internal stop codons in pbp2a due to point mutations or tandem duplications.
• Clinical isolates displayed mosaic pbp2a genes with significant sequence divergence (over 4%) from sensitive strains.
• Most clinical pbp2a variants, except one from South Africa, contained sequences homologous to Streptococcus mitis B6 pbp2a.

Conclusions:

• Distinct genetic mechanisms drive PBP2a alterations in laboratory versus clinical settings of Streptococcus pneumoniae resistance.
• Streptococcus mitis serves as a reservoir for penicillin resistance determinants found in clinical Streptococcus pneumoniae isolates.