Antimicrobial Action

Antimicrobial Action by Cell Membrane Impairment

Various antibiotics (amphotericin B, nystatin and other polyenes, polymyxins, etc.) affect microbial cytoplasmic membrane. If cytoplasmic membrane becomes impaired, the cell is damaged due to membrane disruption followed by macromolecule and ion leakage.Polymyxins affect gram-negative bacteria, and polyenes act against fungi.

Colistin (or polymyxin E) is produced by Paenibacillus polymyxa being composed of cyclic polypeptides. In certain clinical situations, it is the drug of last resort for treatment of infections, caused by multidrug-resistant gram-negative bacteria Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumonia.

Polyenes bind to sterols, which are present in the fungal cell membrane but absent in the bacterial cells. Therefore, polymyxins are inactive against fungi, whereas polyenes are non-efficient against bacteria.

Antimicrobial Action by Protein Synthesis Inhibition

It has been found that a great variety of antibiotics inhibit protein synthesis in bacteria.

Bacteria possess 70S ribosomes, and conversely, mammalian cells use 80S ribosomes. Structural differences provide selective inhibition of bacterial protein synthesis without impairment of host ribosomal apparatus.


Aminoglycosides (streptomycin, gentamycin, amikacin and others) attach to 30S subunit of the bacterial ribosome. Conversion in protein synthesis initiation site leads to incorrect amino acid insertion into newly polymerized protein. Also, aminoglycosides hamper polysomes formation.

The effect is irreversible, that’s why aminoglycosides show bactericidal effect.


Tetracyclines, as well as aminoglycosides, bind to the 30S subunit of microbial ribosomes. Tetracyclines (tetracycline itself, doxycycline and others) inhibit protein synthesis preventing aminoacyl-tRNA attachment to the ribosome. Tetracycline antibiotics possess bacteriostatic activity but have a broad spectrum of action.

The antibiotics from a new class of glycylcyclines are the derivatives of tetracyclines. The member of this promising group tigecycline demonstrates the remarkable efficacy especially against some antibiotic-resistant bacteria, such as Staphylococcus aureus, E. coli or Acinetobacter baumannii.


Chloramphenicol interacts with the 50S subunit of the ribosome. It blocks the binding of new amino acids to the peptide chain due to peptidyl transferase inhibition. It is mostly a bacteriostatic antibiotic.

Macrolides and azalides

Erythromycin is the basic antibiotic in macrolides group. Azalides comprise more advanced drugs (e.g., azithromycin). These drugs bind to 23S rRNA in the 50S subunit of the bacterial ribosome. Probably they impair amino-acyl translocation in protein synthesis. Azalides develop the bactericidal activity.


Lincomycin and its derivative clindamycin are similar in action with macrolides. They attach to the 50S subunit of bacterial ribosomes blocking amino-acyl residue translocation.

Oxazolidinones (linezolid)

Linezolid is the synthetic antibiotic that reacts with 50S subunit of bacterial ribosome within the individual specific binding site. It is active only against gram-positive bacteria. Linezolid is used for the treatment of infections caused by highly resistant microbials, such as MRSA and vancomycin-resistant enterococci (VRE).

Antimicrobial Action by Nucleic Acid Synthesis Inhibition

A substantial part of modern antibiotics acts as nucleic acid synthesis inhibitors. Among them are fluoroquinolones, rifampicin (rifampin), sulfonamides and trimethoprim, and some others.


These are fluorinated derivatives of nalidixic acid. Nalidixic acid does not possess the potent systemic antibacterial effect, being used mainly as a urinary antiseptic drug. Newly synthesized fluoroquinolones (ciprofloxacin, ofloxacin, norfloxacin, levofloxacin and many others) appear to develop remarkable bactericidal activity and low toxicity.

Their mode of action includes the inhibition of bacterial DNA gyrase and topoisomerase that are essential for bacterial DNA replication.

Rifampicin (or rifampin)

These antibiotic suppresses bacterial propagation due to irreversible inhibition of bacterial DNA-dependent RNA polymerase. This way it dampens bacterial RNA synthesis. Rifampicin develops a strong bactericidal effect. It is able to enter phagocytes and other host cells; thus it can kill intracellular microorganisms. It is the first-line drug for the treatment of tuberculosis.