Development of Resistance to Chemotherapeutic Agents

Question 1

What is antimicrobial resistance?

Answer 1

Bacteria strains are said to be resistant to an antimicrobial agent when the MIC or MBC of the agent against the strain is so high that the usual effective dose or concentration of the agent is no longer effective.

Question 2

What are the theories on the origin of resistance.

Answer 2

1. Pre-existing mutants of the resistant strain:
   It supposes that the resistant mutant pre-exists any contact with the antimicrobial agent
   Here inherent endowments of an organism provide it with a natural mechanism of protection against the actions of a particular antibiotics.
2. Resistance due to exposure of organisms to the antibiotics: It is known that bacteria can develop resistance through contact with sub-lethal levels of the antimicrobial agent

Question 3

What are the ways by which bacteria can develop resistance due to contact with an antimicrobial agent?

Answer 3

1. Acquired resistance: This occurs in vivo, in patients during the course of their treatment with particular chemotherapeutic agents. The occurrence of acquired resistance is related to the frequency and inadequacy of antibiotic use.
   A total withdrawal of an agent for a sufficiently long period may reverse the resistance acquired by organisms.
2. Induced resistance: This involves producing strains of microorganisms that are resistant to antimicrobial agents in the laboratory.
   The procedure is usually to grow the bacteria in the presence of increasing sub-inhibitory concentrations of the antimicrobial agents.
3. Cross-resistance: This occurs in situations where a variant strain, by virtue of its resistance to one agent becomes concurrently resistant to other compounds too, even without any prior contact with the other compounds.
   This is almost uniformly true for the tetracyclines.
   Cross resistance rarely occurs between unrelated compounds.
4. Multiple resistance: This occurs when a microorganism develops resistance to different unrelated antimicrobial agents at different times.
   This occurs notably in resistant strains of the Staphylococci

Question 4

What are the two mechanisms of bacterial resistance?

Answer 4

1. Biochemical basis of resistance
2. Genetic basis of resistance

Question 5

Explain the biochemical basis of bacterial resistance.

Answer 5

i. Modification of the target enzyme in the cell so that it becomes insensitive to the inhibitor, and yet still able to carry out its normal physiological functions.

ii. Reduction of physiological importance of the target enzyme

iii. Provision of permeability changes against the antibiotics e.g. reduction of cellular uptake of the antibiotics or increased efflux of antibiotics from the cell.

iv. Synthesis of an enzyme that is capable of inactivating the inhibitor e.g. β-lactamases Penicillinase and cephalosporinases

Question 6

Explain the genetic basis of bacterial resistance.

Answer 6

Gene mutation can occur spontaneously or by induction. Mutation of pre-existing gene may lead to biosynthesis of a modified target organ.

Bacterial cells can accept large pieces of genetic materials from other bacteria.They can take in and express genetic information that has been evolved and refined elsewhere.
This additional gene may confer resistance against a number of antibiotics.
If the chromosome carrying the additional gene is attached to the original chromosome of the cell, the acquired gene is called chromosomal additional gene.

If not, it is called extra chromosomal additional gene.

Question 7

About plasmids, answer true or false.

i. Also known as resistance (R) factor, they are responsible for the resistance of bacteria to antibiotics.

ii. They are chromosomal addition genes.

iii. It is capable of replicating itself independent of the original gene of the cell.

iv. By continuous replication, it transforms itself to the dominant gene of the cell.

v. It is self-transmissible.

Answer 7

i. True
ii. False. They are extra chromosomal additional gene
iii. True
iv. True
v. True

Question 8

What are the modes of inter-cellular transmission of genes?

Answer 8

1. Conjugation: This involves the joining of two cells by means of their pili
   The R factor is transferred through a cytoplasmic bridge thus formed from the donor cell to the recipient cell.
2. Transformation: This is a process in which water soluble fragments of DNA are transferred from a donor cell to a recipient cell through an aqueous medium.
3. Transduction: In this process, a small portion of the chromosomal DNA is introduced into the recipient cell by a temperate bacteriophage, which has been formed in the donor cell.
   The transduced gene is incorporated into the host cell’s gene as a prophage

Question 9

Mention 7 ways by which bacterial resistance can be controlled.

Answer 9

1. Restricting the use of antibiotics.
2. Reduction of systemic use of antibiotics for prophylaxis.
3. Adequate dosage of effective antibiotics.
4. Control of the spread of infections.
5. Use of antibiotics against which resistance rarely or never emerges.
6. Use of combined chemotherapy.
7. Rational use of antibiotics.
8. Maintenance of adequate surveillance on the incidence of resistance bacteria.
9. Use of antiseptics rather than antibiotics for local prophylaxis.
10. Introduction of vaccines against various pathogens.
11. Inhibition of bacterial enzymes that inactivates antibiotics.