Antibiotics - Mode of Action

   The antibiotics are the chemotheraputic agents. The target of antibiotics are microorganisms more precisely bacteria. once treated with the correct antibiotics the bacterial infection is eliminated. In general antibiotics do not function against viruses or fungi instead they are specifically directed against bacteria.

  The first antibiotic was discovered by Sir Alexander Fleming in 1928. He observed a spot in his petri dish where bacteria(staphylococcus aureus) did not grow around fungi(Penicillium notatum). These fungi produced an antibacterial substance which killed the surrounding microbes. It is commonly known under the term penicillin. This discovery is often described as one of the greatest victories ever achieved over disease.

General Mode of Action of Antibiotics

  The antibiotics act in general by killing the pathogen or inhibiting their growth. This is achieved by following general modes of attack.
  1. By Inhibition of cell wall synthesis.
  2. By Inhibition of protein synthesis.
  3. By Interfering with nucleic acid synthesis.
  4. By interfering with cell membrane structure and function.
  5. By inhibition specific enzyme system of the cell.

Inhibition of cell wall synthesis

  Many Antibiotics are able to act by inhibiting the synthesis of peptidoglycan of bacterial cell wall.
  Peptidoglycan is the principal chemical constituent of the bacterial cell walls. Inhibition of synthesis of peptidoglycan, therefore, Interferes with the formation of new cell wall.

  Thus, if the bacteria are allowed to grow in presence of the agents that Inhibit peptidoglycan synthesis, cells will continue to grow and divide, but without formation of new cell wall material. As a result, the cells will be ultimately converted Into spheroplasts and protoplasts.

  These, spheoplasts and protoplasts are highly fragile and get lysed. Thus, the cells, growing in presence of agents inhibiting cell wall synthesis are lysed.

  Since, peptidoglycan is found only in bacteria and not in other cukaryotic cells, these agents possess selective toxicity for bacteria and become sultable for the chemotherapeutic application.

  Further, these antibiotics are usually more effective on gram- positive bacteria. This is due to the higher content of peptidoglycan in cell walls of gram-positive bacteria as compared to gram-negative bacteria.
  The table shows different antibiotics inhibiting peptidoglycan synthesis at different stages of its biosynthesis.

Antibiotics Inhibiting cell wall biosynthesis

Inhibition of protein synthesis

  Proteins are important constituent of all living cells. They may be

  • Structural proteins, being part of various cell structures.
  • Functional proteins, mainly enzymes, responsible for various metabolic activities performed by cells.

Inhibition of protein synthesis, therefore, results into the inhibition of growth of microorganisms.

 Synthesis of proteins takes place on ribosome involving following major steps. 

  1. Charging of tRNA with amino acids.
  2. Formation of mRNA-ribosome complex.
  3. Binding of aminoacyl tRNA to ribosome.
  4. Formation of peptide bond involving a peptidal transfer reaction where a new amino acid is transferred from aminoacyl tRNA to a growing peptide chain.
  5. Translocating step where deacylated tRNA is removed from ribosome and site is made vacant for new aminoacyl tRNA to bind on ribosome so that the cycle leading to growth of peptide chain continues.
  6. Release of grown peptide chain from ribosome, when complete mRNA is translated. This signal for termination of protein synthesis is provided by nonsense codons of mRNA. This is followed by dissociation of ribosome and mRNA.

  This shows that any agent, which can bind with ribosome, will be able to inhibit protein synthesis. Most antibiotics, capable of inhibiting protein synthesis are able to bind either 30S or 50S submit of 70S ribosome of prokaryotes. Eukaryotes have 80S ribosome.

  These antibiotics are not able to bind with them and hence do not interfere with their functioning. Thus, the antibiotics affecting protein synthesis have selective toxicity for bacteria and therefore, they possess chemotherapeutic value.
  Table shows various antibiotics that inhibit protein synthesis at difference stages.

Examples of Antibiotics interfering protein synthesis

Inhibition of nucleic acid synthesis

  Like proteins, nucleic acids are also vital macromolecules of cells. Two classes of nucleic acids occur in cell.
  1. RNA, which mainly participate in the protein biosynthesis.
  2. DNA, which carries the entire genetic information for the characters to be expressed by the organisms. by acting as the hereditary material.
  Inhibition of the synthesis of nucleic acids is, therefore, able to inhibit the growth of microorganisms.

1) Inhibition of RNA synthesis

  Certain antibiotics are able to bind with the key enzyme involved in RNA synthesis; RNA polymerase. Bindings of antibiotics to this enzyme Interfere with the functioning of the enzyme and prevent RNA synthesis. e.g. rifamycin and rifampicin.

Certain other antibiotics bind with GC pair of the DNA and prevent unfolding of DNA. required for transcription (RNA synthesis). Thus, they Inhibit RNA synthesis. e.g. Mitomycin C, Actinomycin D.

2) Inhibition of DNA synthesis

  Certain antibiotics are able to inhibit replication of chromosomal DNA, by
  • binding to the enzyme DNA polymerase, required for chromosome replication or
  • binding to GC pair of DNA and prevent its unfolding. essential for DNA replication.

 Table summarizes agents that inhibit Nucleic acid synthesis.

Antibiotics targeting nucleic acid synthesis and functioning

Damage to cytoplasmic membrane

  Certain chemotherapeutic agents are able to inhibit or kill the microorganisms by damaging the functioning of cell membrane. Cell membrane is a selectively permeable membrane and it maintains concentration of the cytoplasm by control of entry and exit of molecules across the membrane.

  Binding of agents to cell membrane, therefore, interferes with cell's permeability barrier and causes leakage of cellular molecules, leading to cell's death. These antibiotics possess toxicity to tissues. Therefore they have limited application in chemotherapy.
e.g. Polymyxins, Gramicidin. Tyrocidines. Nystatin, Amphotericin B.

Inhibition of specific enzyme system

  Certain chemotherapeutic agents are able to bring about inhibition of a specific enzyme reaction, which may be essential for the operation of a specific biochemical pathway leading to the biosynthesis of a vital substance essential for the growth.

Inhibition of this pathway, therefore, deprives cell from availability of this vital substance essential for growth (which may be a vitamin, amino acid, coenzyme etc.). As a result, the growth of organisms is inhibited. 

  Table summarizes some of such chemotherapeutic agents.

Examples of Antibiotics agent targeting action of enzyme