M07.07.02 Mechanisms of Antibiotic Action

Antibiotics exert their therapeutic effects by targeting specific cellular processes essential for bacterial survival and growth. Understanding the diverse mechanisms of antibiotic action is crucial for selecting appropriate antibiotics and combating bacterial infections effectively.

Inhibition of Cell Wall Synthesis:

• Beta-lactam antibiotics, such as penicillins and cephalosporins, inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to the disruption of peptidoglycan cross-linking and eventual cell lysis.
• Glycopeptide antibiotics, like vancomycin, inhibit cell wall synthesis by binding to the D-alanyl-D-alanine terminus of peptidoglycan precursors, preventing their incorporation into the growing cell wall.

Inhibition of Protein Synthesis:

• Aminoglycoside antibiotics, such as gentamicin and streptomycin, bind to the 30S ribosomal subunit, causing misreading of mRNA and inhibiting protein synthesis.
• Macrolide antibiotics, like erythromycin and azithromycin, bind to the 50S ribosomal subunit, preventing the translocation of peptidyl-tRNA and inhibiting protein synthesis.

Inhibition of Nucleic Acid Synthesis:

• Quinolone antibiotics, such as ciprofloxacin and levofloxacin, target bacterial DNA gyrase and topoisomerase IV, inhibiting DNA replication and transcription.
• Rifamycin antibiotics, like rifampin, inhibit bacterial RNA synthesis by binding to the β-subunit of bacterial RNA polymerase, blocking the initiation of RNA synthesis.

Disruption of Cell Membrane Integrity:

• Polymyxin antibiotics, such as polymyxin B and colistin, disrupt bacterial cell membrane integrity by interacting with lipopolysaccharides in the outer membrane of Gram-negative bacteria, leading to cell leakage and death.

Inhibition of Metabolic Pathways:

• Sulfonamide antibiotics, like sulfamethoxazole, and trimethoprim inhibit bacterial folate synthesis by blocking enzymes involved in the synthesis of tetrahydrofolate, essential for nucleic acid synthesis.
• Metronidazole, a nitroimidazole antibiotic, disrupts bacterial DNA synthesis by forming toxic metabolites that damage bacterial DNA.

Efflux Pump Inhibition:

• Some antibiotics inhibit bacterial efflux pumps, which are responsible for extruding antibiotics out of bacterial cells, thereby enhancing the intracellular concentration of antibiotics and overcoming resistance mechanisms.

Understanding the mechanisms of antibiotic action is essential for rational antibiotic use, optimizing treatment outcomes, and combating antibiotic resistance. By targeting specific bacterial vulnerabilities, antibiotics can effectively eradicate bacterial infections and restore patient health. However, the emergence of antibiotic resistance underscores the importance of antibiotic stewardship and the development of novel antibiotics to address evolving bacterial threats.