Question

23. Various antimicrobial therapeutics target protein synthesis and are safe to uses in humans. Protein synthesis is essential in both microbes and in humans. Why do you think they are safe to use for medicinal purposes in humans? (500 words)

Answer 1

Ans.

• Antimicrobials agents are the chemicals that inhibit or kill prokaryotic (microorganisms) cells but do not harm eukaryotic cells.
• These agents include both, natural as well as artificial chemical agents.
• Natural antimicrobial agents are produced mostly by bacterias and fungi for eg. production of penicillin from penicillium notatum.
• A large number of compounds that have antibiotic activity, have been obtained from the microbes over a time period of several decades.
• But only a handful of antibiotics are useful in clinical settings for a simple reason that is that only those compounds can be used clinically that have selective toxicity.
• The high selectivity of antimicrobial agents implies that they must show high activity against the invading microorganisms but should show no to minimal toxicity to humans.
• This selectivity can be determined by the therapeutic index of a drug.
• Therapeutic index (TI) of a drug refers to the ratio of toxic dose (harmful to the patient) to the therapeutic dose (effective for treating the infection) of a drug.
• The greater the therapeutic index, the safer and nontoxic the drug for use in humans.
• Finding the vulnerable drug targets in microorganisms that are not present in the animal cells forms the basics of selective toxicity of antibiotics.
• Key targets of antibiotics action in clinical settings include components in bacterias that are unique to them such as bacterial cell wall synthesis, synthesis of proteins in bacterias and synthesis of nucleic acids in bacterias.
• A classic example of antibiotic action is inhibition of peptidoglycan synthesis in the cell wall of bacteria by the beta lactam antibiotics.
• Since, cell wall and peptidoglycan are absent in humans, so they remain unaffected by the action of these drugs.
• Some antibiotics, such as streptomycin and tetracyclines, can selectively affect bacterial protein synthesis due to difference between bacterial ribosomes (70S) and human ribosomes (80S) and ribosomes of other eukaryotic organisms.
• Selective toxicity is the most important characteristic of an antimicrobial agent from the perspective of patients.
• Following are the characteristics of an ideal and clinically useful antimicrobial agent;

1. Must posses a wide spectrum of activity and be able to inhibit or kill a large number of different microbes species.
2. Should not show any toxicity to the host with minimal to no undesirable adverse effects.
3. Should not show any allergic reaction to the host.
4. It should not affect the normal microbial population of host.
5. It must be reachable to the infected body part of host.
6. It must show chemical stability.
7. Low degree of resistance development.

• Some examples of antimicrobial agents are -

1. Beta lactams - examples include penicillin G and cephalothin that works by inhibiting the steps of cell wall synthesis in microbes.
2. Aminoglycosides - an example is streptomycin that inhibits protein synthesis in bacterias.
3. Glycopeptides - vancomycin is an example that inhibit steps of murein synthesis and assembly in microbes.
4. Macrolides - an example is erythromycin that inhibit steps of translation in bacterias.
5. Tetracyclines - act by inhibiting protein synthesis in bacterias.
6. Flouoroquinolones - act by inhibiting DNA replication in bacterias.