Cell Wall Synthesis Inhibitors
The bacterial cell wall consists of a unique component — peptidoglycan. Because this substance is absent in the human body, drugs in this group exhibit high selectivity.
The process of wall formation begins with the synthesis of precursors in the cytoplasm; they are then transported across the membrane and incorporated into the cell wall.
- Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) bind to penicillin-binding proteins (PBPs), which are responsible for the final assembly of peptidoglycan on the outer surface of the membrane. An excess of unused precursors accumulates in the cell, serving as a signal to activate autolytic enzymes (autolysins). Normally required for division, their excess literally dissolves the wall, causing bacterial death (lysis).
- Glycopeptides (vancomycin, teicoplanin) interrupt the process at the stage of precursor transport and incorporation.
- Other agents, such as cycloserine and bacitracin, are more toxic and are therefore kept in reserve or used only topically.
Protein Synthesis Inhibitors
This group of antibiotics exploits the structural difference in ribosomes: prokaryotes possess 70S ribosomes (consisting of 30S and 50S subunits), which distinguishes them from human ribosomes.
- Action on the 30S subunit: Aminoglycosides irreversibly impair the formation of the initiation complex and aminoacyl-tRNA attachment, blocking translation initiation. Tetracyclines act similarly, but they reversibly block the binding of aminoacyl-tRNA to the acceptor site.
- Action on the 50S subunit: Macrolides (erythromycin), chloramphenicol, and lincosamides block the enzyme peptidyl transferase and disrupt the translocation of peptidyl-tRNA. This terminates the elongation of the protein chain. The effect is bacteriostatic: if the antibiotic is removed, the microorganism resumes synthesis.
- Other mechanisms: Fusidic acid halts chain elongation, while oxazolidinones block the very possibility of joining the two subunits into a single 70S complex and disrupt the release of the completed peptide chain.
Nucleic Acid Synthesis Blockers
These chemotherapeutic agents interfere with bacterial nucleic acid metabolism at three different metabolic levels:
- Blockade of precursor synthesis (antimetabolites): Sulfonamides and trimethoprim deprive the cell of purine and pyrimidine bases. Structurally, sulfonamides are analogues of para-aminobenzoic acid (PABA). They competitively bind the enzyme that converts PABA into folic acid, thereby halting nucleic acid synthesis.
- Suppression of DNA functions: Fluoroquinolones/quinolones bind to the enzyme DNA gyrase and inactivate it, blocking normal DNA replication. Nitroimidazoles and nitrofurans also belong to this group.
- Halt of transcription (RNA synthesis): Rifamycins (the only natural antibiotics in this group) attach to RNA polymerase and block messenger RNA synthesis.
Disruption of Cytoplasmic Membrane Function
The cytoplasmic membrane is present in all cells — bacteria, fungi, and humans. Consequently, drugs in this group exhibit low selective toxicity.
- Antibacterial agents: The primary representative is polymyxins (polypeptides). They act exclusively on Gram-negative bacteria, damaging membrane phospholipids and causing lysis. Due to their extremely high toxicity in humans, they are currently rarely used systemically.
- Antifungal agents: Fungal cells are evolutionarily much closer to human cells than bacteria are, which is why systemic antifungals are very limited. Their main target is ergosterol, a specific component of the fungal membrane. Polyene antibiotics directly bind and disrupt ergosterols, whereas azoles inhibit the enzymes required for their biosynthesis.