Question

xplain how antibiotic resistance develops from a population of susceptible bacteria.

Answer 1

The resistance which is developed in susceptible bacteria is known as acquired resistance.

Mutation:
It is the development of resistance by an organism (which was sensitive before) due to the use of an AMA over a period of time. This can happen with any microbe and is a major clinical problem. However, development of resistance is dependent on the microorganism as well as on the drug. Some bacteria are notorious for rapid acquisition of resistance, e.g. staphylococci, coliforms, tubercle bacilli. Others like Strep. pyogenes and spirochetes have not developed significant resistance to penicillin despite its widespread use for > 50 years.
Gonococci quickly developed resistance to sulfonamides, but only slowly and low-grade resistance to penicillin. However, in the past 40 years, highly penicillin resistant gonococci producing penicillinase have appeared. Resistance may be developed by mutation or gene transfer.
Mutation It is a stable and heritable genetic change that occurs spontaneously and randomly among microorganisms. Any sensitive population of a microbe contains a few mutant cells which require higher concentration of the AMA for inhibition. These are selectively preserved and get a chance to proliferate when the sensitive cells are eliminated by the AMA. Thus, in time
it would appear that a sensitive strain has been replaced by a resistant one, e.g. when a single antitubercular drug is used. This is called vertical transfer of resistance; is relatively slow and usually of lower grade. Mutation and resistance may be:
(i) Single step: A single gene mutation may confer high
degree of resistance; emerges rapidly, e.g. enterococci to
streptomycin, E. coli and Staphylococci to rifampin.
(ii) Multistep: A number of gene modifications are involved;
sensitivity decreases gradually in a stepwise manner.
Resistance to erythromycin, tetracyclines and chloramphenicol is developed by many organisms in this manner. Sometimes mutational acquisition of resistance is
accompanied by decrease in virulence, e.g. certain rifampin-resistant staphylococci and low grade penicillin-resistant gonococci have decreased virulence.

Gene transfer:

The resistance causing gene is passed from one organism to the other; is called horizontal transfer of resistance. Rapid spread of resistance can occur by this mechanism and high level resistance to several antibiotics (multidrug
resistance) can be acquired concurrently.

There are three mechanism of Gege transfer

a. Conjugation: Sexual contact through the formation of
a bridge or sex pilus is common among gram-negative bacilli of the same or another species. This may involve chromosomal or extrachromosomal (plasmid) DNA. The gene carrying the ‘resistance’ or ‘R’ factor is transferred only if another ‘resistance transfer factor’ (RTF) is also present. Conjugation frequently occurs in the colon where a large variety of gramnegative bacilli come in closecontact. Even nonpathogenic organisms may transfer R factor to pathogenic organisms, which may become widespread by contamination of food or water. Chloramphenicol resistance of typhoid bacilli, streptomycin resistance of E. coli, penicillin resistance of Haemophilus and gonococci and many others have been traced to this mechanism.
(ii) Transduction: It is the transfer of gene carrying
resistance through the agency of a bacteriophage. The R
factor is taken up by the phage and delivered to another
bacterium which it infects. Many Staph. aureus strains have acquired resistance by transduction. Certain instances of penicillin, erythromycin and chloramphenicol resistance have been found to be phage mediated.
(iii) Transformation: A resistant bacterium may release the resistance carrying DNA into the medium and this may be imbibed by another sensitive organism—becoming
unresponsive to the drug. This mechanism is probably not
clinically significant.
Resistance once acquired by any of the above mechanisms becomes prevalent due to theselection pressure of a widely used AMA, i.e. presence of the AMA provides opportunity for the resistant subpopulation to thrive in preference to the sensitive population.