Related Experiment Videos
Resistant penicillin-binding proteins
1Institut für Mikrobiologie, Universität Kaiserslautern, Germany. hakenb@rhrk.uni-kl.de
Abstract:
Low-affinity penicillin-binding proteins (PBPs), which participate in the beta-lactam resistance of several pathogenic bacteria, have different origins. Natural transformation and recombination events with DNA acquired from neighbouring intrinsically resistant organisms are responsible for the appearance of mosaic genes encoding two or three low-affinity PBPs in highly resistant strains of transformable microorganisms such as Neisseria and Streptococcus pneumoniae. Methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococcal strains possess the mecA determinant gene, which probably evolved within the Staphylococcus genus from a closely related and physiologically functional gene that was modified by point mutations. The expression of mecA is either inducible or constitutive. A stable high-level resistant phenotype requires the synthesis of a normally constituted peptidoglycan. Enterococci have a natural low susceptibility to beta-lactams related to the presence of an intrinsic low-affinity PBP. Highly resistant enterococcal strains overexpress this PBP and/or reduce its affinity.
Insights
Diverse origins of low-affinity penicillin-binding proteins (PBPs) drive beta-lactam resistance in bacteria. Mechanisms include natural transformation in Neisseria and Streptococcus, and mecA gene evolution in Staphylococcus, alongside intrinsic PBP modifications in Enterococcus.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Low-affinity penicillin-binding proteins (PBPs) are key determinants of beta-lactam antibiotic resistance in various pathogenic bacteria.
- Understanding the evolutionary origins and genetic mechanisms of these PBPs is crucial for combating antimicrobial resistance.
Purpose of the Study:
- To elucidate the diverse origins and genetic mechanisms underlying the emergence of low-affinity PBPs responsible for beta-lactam resistance.
- To differentiate the evolutionary pathways of low-affinity PBPs in distinct bacterial genera.
Main Methods:
- Comparative genomics and sequence analysis to investigate the evolutionary history of PBP genes.
- Molecular studies to understand the genetic basis of PBP modification and expression.
- Phenotypic analysis of bacterial resistance mechanisms related to PBP alterations.
Main Results:
- Mosaic PBP genes in Neisseria and Streptococcus pneumoniae arise from natural transformation and recombination with external DNA.
- The mecA gene in Staphylococcus aureus evolved through point mutations from a native, functional gene within the Staphylococcus genus.
- Enterococci exhibit natural low beta-lactam susceptibility due to intrinsic low-affinity PBPs, with resistance enhanced by overexpression or reduced affinity.
Conclusions:
- Beta-lactam resistance mediated by low-affinity PBPs is driven by distinct evolutionary strategies across different bacterial species.
- Genetic mechanisms range from horizontal gene transfer and recombination to point mutations and altered gene expression.
- Targeting these diverse PBP origins and mechanisms is essential for developing effective strategies against antibiotic resistance.