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Related Experiment Videos

Resistant penicillin-binding proteins

R Hakenbeck1, J Coyette

  • 1Institut für Mikrobiologie, Universität Kaiserslautern, Germany. hakenb@rhrk.uni-kl.de

Cellular and Molecular Life Sciences : CMLS
|June 6, 1998
PubMed
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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.

Related Experiment Videos

  • 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.