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Penicillin-binding proteins in Streptococcus pneumoniae: alterations during development of intrinsic penicillin
R Hakenbeck1, T Briese, G Laible
1Max-Planck Institut für molekulare Genetik, Berlin, Germany.
Abstract:
Four out of the five high molecular weight penicillin-binding proteins (PBPs) of Streptococcus pneumoniae are involved in the development of intrinsic penicillin resistance. In beta-lactam resistant laboratory mutants, point mutations in the PBP 2x-genes were identified that result in low penicillin-affinity mutant proteins. In contrast, PBPs 1a, 2x, and 2b of resistant clinical isolates are highly altered as can be recognized biochemically and immunologically; DNA sequence analysis of the PBP 2x gene from resistant strains confirmed these results. The variability of the three PBPs analyzed implies a very heterogeneous gene pool accessible to the pneumococcus that is used for recruitment of resistant PBP genes in wild type strains.
Insights
Penicillin resistance in Streptococcus pneumoniae involves high molecular weight penicillin-binding proteins (PBPs). Resistant strains show significant alterations in PBPs 1a, 2x, and 2b, indicating a diverse gene pool for resistance development.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Four of five high molecular weight penicillin-binding proteins (PBPs) in Streptococcus pneumoniae contribute to intrinsic penicillin resistance.
- Penicillin resistance is a growing concern in pneumococcal infections.
Purpose of the Study:
- To investigate the molecular mechanisms and genetic basis of penicillin resistance in Streptococcus pneumoniae.
- To analyze alterations in penicillin-binding proteins (PBPs) in resistant strains.
Main Methods:
- Biochemical and immunological characterization of PBPs in resistant clinical isolates.
- DNA sequence analysis of the PBP 2x gene from resistant Streptococcus pneumoniae strains.
- Comparison of PBP alterations in laboratory mutants versus clinical isolates.
Main Results:
- Point mutations in PBP 2x-genes were found in beta-lactam resistant laboratory mutants, leading to low penicillin-affinity mutant proteins.
- PBPs 1a, 2x, and 2b from resistant clinical isolates exhibited significant biochemical and immunological alterations.
- DNA sequencing confirmed the extensive modifications in the PBP 2x gene of resistant strains.
Conclusions:
- The high degree of variability in PBPs 1a, 2x, and 2b suggests a highly heterogeneous gene pool utilized by Streptococcus pneumoniae.
- This genetic diversity facilitates the acquisition of resistant PBP genes by wild-type strains, contributing to the spread of penicillin resistance.