Cell wall synthesis inhibitors
The bacterial cell wall consists of a unique component — peptidoglycan. Since this substance is absent in the human body, drugs of this group exhibit high selectivity.
The wall formation process begins with the synthesis of precursors in the cytoplasm, after which they are transported across the membrane and incorporated into the cell wall.
- Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) block penicillin-binding proteins (PBPs), which are responsible for the final assembly of peptidoglycan on the outer side of the membrane. An excess of unused precursors accumulates in the cell, signaling the activation of autolytic enzymes (autolysins). Normally, these are required for cell division, but when present in excess, they literally dissolve the cell 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, which is why they remain in reserve or are used only topically.
Protein synthesis inhibitors
Antibiotics of this group exploit differences in ribosome structure: in prokaryotes, they are of the 70S type (consisting of 30S and 50S subunits), which distinguishes them from human ribosomes.
- Effect on the 30S subunit: Aminoglycosides irreversibly disrupt the formation of the initiation complex and the attachment of transfer RNA, blocking the start of synthesis. Tetracyclines act similarly, but they reversibly block the binding of aminoacyl-tRNA to the acceptor site.
- Effect on the 50S subunit: Macrolides (erythromycin), chloramphenicol, and lincosamides block the enzyme peptidyl transferase and disrupt the translocation of peptidyl-tRNA. This halts the elongation of the protein chain. The effect is bacteriostatic: if the antibiotic is removed, the microorganism will resume synthesis.
- Other mechanisms: Fusidic acid halts chain elongation, while oxazolidinones block the very possibility of combining the two subunits into a single 70S complex and disrupt the release of the finished chain.
Nucleic acid 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 p-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 disable it, blocking normal DNA replication. Nitroimidazoles and nitrofurans belong to the same group.
- Halting transcription (RNA synthesis): Rifamycins (the only natural antibiotics in their group) attach to RNA polymerase and block messenger RNA synthesis.
Disruption of cytoplasmic membrane function
The cytoplasmic membrane (CPM) is present in all cells — bacteria, fungi, and humans alike. Consequently, drugs of this group exhibit low selective toxicity.
- Antibacterial agents: The main representatives are polymyxins (polypeptides). They act exclusively on gram-negative bacteria by damaging membrane phospholipids, which causes lysis. Due to extremely high toxicity to humans, they are currently almost never used in systemic practice.
- Antifungal agents: Fungal cells are evolutionarily much closer to human cells than bacteria are, which is why systemic antifungals are very few in number. Their main target is ergosterol, a specific component of the fungal membrane. Polyene antibiotics directly destroy ergosterols, while imidazoles inhibit the enzymes required for their biosynthesis.
Briefly: answers to topical questions
Which enzymes do sulfonamides block?
Sulfonamides block the enzyme dihydropteroate synthase (also referred to as dihydropteroate synthetase). This enzyme normally catalyzes the condensation of p-aminobenzoic acid (PABA) with dihydropteridine to form dihydropteroic acid, a precursor of folic acid. Enzyme blockade occurs via competitive inhibition, as sulfonamides are structural analogues of PABA. As a result of competition for the active site of the enzyme, the synthesis of purines and pyrimidines, which are vital for bacteria, is disrupted.
Which antibiotics exhibit a bactericidal type of action?
The following groups of antibiotics exhibit a bactericidal type of action, causing microbial death through irreversible damage to their structures:
- Beta-lactams — penicillins, cephalosporins, carbapenems, and monobactams.
- Rifamycins — specifically, rifampin.
- Polypeptides — polymyxins.
What are the mechanisms of bacterial resistance to macrolides?
Bacterial resistance to macrolides is mediated through four main mechanisms.
- Enzymatic inactivation — production of esterases that hydrolyze the drug (characteristic of enterococci).
- Target modification — alteration of the ribosomal binding site structure through chromosomal mutations or the production of methylase enzymes (the primary mechanism in Gram-positive bacteria).
- Impaired transport — decreased cell membrane permeability or active efflux of the drug from the cell.
- Cross-resistance — constitutive production of methylase provides resistance to macrolides, lincosamides, and streptogramins B (MLS phenotype).
It is easy to remember the nature of action of protein inhibitors: drugs acting on the 50S ribosomal subunit exert a bacteriostatic effect (merely arresting growth), whereas those acting on the 30S subunit (e.g., aminoglycosides) can bind irreversibly.
Class and exam questions
Why are penicillins ineffective against mycoplasmas?
Mycoplasmas naturally lack a cell wall (peptidoglycan). Since the target for beta-lactam antibiotics is completely absent in them, these drugs are powerless against them.
What is the main danger of antifungal drugs?
Fungal cell membranes are significantly closer in structure to human cell membranes than to bacterial ones. Consequently, antifungals exhibit high cross-toxicity.
How exactly do beta-lactam antibiotics kill the cell?
They do not dissolve the wall themselves, but rather block penicillin-binding proteins. The accumulation of excess building material (precursors) sends a false signal to the cell to trigger its self-destruction system — autolytic enzymes, which ultimately destroy the bacterium.
What else to study on this topic
- Structural features of prokaryotic (70S) versus eukaryotic ribosomes
- Mechanism of activation of bacterial autolytic enzymes
- The principle of competitive inhibition using PABA and sulfonamides as an example
- The role of DNA gyrase in bacterial chromosome supercoiling
Study the full topic in the «Microbiology» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Mechanisms of Action of Antimicrobial Agents" and 4,383 other subject pages
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 141 video lectures on the subject
Other topics in the section "Chemotherapeutic Antimicrobial Drugs"
Free video lessons: microbiologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.