Cell Wall Inhibitors

Cell Wall Inhibitors

Overview

  • Antimicrobial drugs can selectively interfere with bacterial cell wall synthesis, a structure absent in mammalian cells.

  • The cell wall is composed of peptidoglycan, a polymer of glycan units joined by peptide cross-links.

  • Inhibitors of cell wall synthesis are most effective against actively proliferating microorganisms and have limited effect on non-growing bacteria.

  • Key drugs in this group include β-lactam antibiotics and vancomycin.

  • β-lactam antibiotics are named for the β-lactam ring, which is crucial for their activity.

Penicillins

  • Penicillins are highly effective and relatively non-toxic, but increasing resistance has limited their use.

  • They differ in the R substituent attached to the 6-aminopenicillanic acid residue.

  • The side chain (R group) affects antimicrobial spectrum, stability to stomach acid, cross-hypersensitivity, and susceptibility to bacterial degradative enzymes (β-lactamases).

Mechanism of Action

  • Penicillins interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linkage), exposing the osmotically less stable membrane.

  • This leads to cell lysis due to osmotic pressure or activation of autolysins, making them bactericidal.

  • Effectiveness depends on the antibiotic's size, charge, and hydrophobicity.

  • Effective only against rapidly growing organisms with peptidoglycan cell walls.

  • Inactive against organisms lacking this structure, such as mycobacteria, protozoa, fungi, and viruses.

  1. Penicillin-Binding Proteins (PBPs):

    • Penicillins inactivate various proteins on the bacterial cell membrane, known as PBPs.

    • PBPs are bacterial enzymes involved in cell wall synthesis and maintaining bacterial morphology.

    • Exposure can prevent cell wall synthesis and cause morphological changes or lysis.

    • The number of PBPs varies with the type of organism.

    • Alterations in PBPs can lead to penicillin resistance; for example, Methicillin-resistant Staphylococcus aureus (MRSA).

  2. Inhibition of Transpeptidase:

    • PBPs catalyze the formation of cross-linkages between peptidoglycan chains.

    • Penicillins inhibit this transpeptidase-catalyzed reaction, hindering cross-link formation essential for cell wall integrity.

    • This blockade leads to the accumulation of