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

Alterations in PBP2a have been recognized in cefotaxime-resistant laboratory mutants and β-lactam-resistant clinical isolates of Streptococcus pneumoniae. DNA sequencing revealed fundamental differences between these two settings. Internal stop codons in pbp2a occurred in all three laboratory mutants analyzed, caused by a mutation in pbp2a of mutant C604, and tandem duplications within pbp2a resulting in premature stop codons in another two mutants C403 and C406. In contrast, mosaic PBP2a genes were observed in several penicillin-resistant clinical isolates from South Africa, the Czech Republic, Hungary, and in the clone Poland23F-16, with sequence blocks diverging from sensitive strains by over 4%. Most of these pbp2a variants except pbp2a from the South African strain contained sequences related to pbp2a of Streptococcus mitis B6, confirming that this species serves as reservoir for penicillin-resistance determinants.