• Penicillins

  • β-Lactamase Inhibitors (Introduction to Penicillins)

    Beta-Lactamase Inhibitors Audio Overview

     

    • Overview

      • Penicillins are class of antibiotics that act by interfering with bacterial cell wall synthesis.^1,2 

        • These antibiotics inhibit peptidoglycan formation, structural essentials of bacterial cell walls.

        • Penicillin Mechanism

          Attribution Bradleyhintze, CC0, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Simple_penicillin_mechanism.png 28 July 2013.

       

      • Inhibition occurs because penicillins resemble part of the peptide precursor normally recognized by transpeptidases (also known as penicillin-binding proteins or PBPs).

        • Transpeptidases are responsible for catalyzing cross-linking of peptidoglycan chains.

        • Cross-linking these chains provide both stability and rigidity to the bacterial cell wall.

        • Penicillin-binding to the active site of transpeptidases prevents this cross-linking process by irreversibly inactivating the enzymes.

        • Because of this inactivation, the weekend and unstable bacterial cell wall will lack the structural integrity needed to withstand osmotic pressure and as result eventually lyse.

      • Beta-lactamases are bacterial enzymes that confer resistance to ß-lactam antibiotics, such as penicillins.

        • The beta-lactamases work by hydrolyzing the ß-lactam ring which is critical structural element present in all penicillins and related antibiotics such as carbapenems and cephalosporins.

          • Attribution Beta-lactam Pharmacology (Last modified May 4, 2025 by cclarks) Pharmwiki https://tmedweb.tulane.edu/pharmwiki/doku.php/betalactam_pharm

        • Cleavage of the ß-lactam ring results in an inactive penicillin molecule since it can no longer bind in inhibit transpeptidase enzymes.

        • This enzymatic inactivation represents the primary mechanism by which bacterial resistance to penicillin antibiotics develops.

      • Genes encoding ß-lactamases are found on bacterial plasmids, mobile genetic elements easily transferable between bacteria.

      • This "horizontal" gene transfer contributes to the rapid spread of antibiotic resistance in bacteria populations.

      • In order to overcome this resistance mechanism, some penicillin formulations include ß-lactamase inhibitors that bind to and inactivate ß-lactamase enzymes, consequently protecting coadministered penicillin.

August, 2025