Genetic Mechanism of Drug Resistance
| A | Resistance is produced as a result of alteration in Penicillin Binding Proteins (PBP) | |
| B |
Resistance is produced by production of beta lactamase |
|
| C |
Resistance is mediated by plasmids |
|
| D |
Expression of resistance is enhanced by incubating at 37°C during susceptibility testing |
Which of the following statements is most correct regarding resistance to methicillin in MRSA-
| A |
Resistance is produced as a result of alteration in Penicillin Binding Proteins (PBP) |
|
| B |
Resistance is produced by production of beta lactamase |
|
| C |
Resistance is mediated by plasmids |
|
| D |
Expression of resistance is enhanced by incubating at 37°C during susceptibility testing |
Ans. is ‘a’ i.e., Resistance is produced as a result of alteration in Penicillin Binding Proteins
o Resistance in MRSA is mainly produced by the presence of an altered penicillin binding protein.
o Resistance may also be produced by hyperproduction of beta-lactamase. But this is very rare.
o Resistance is mediated by chromosome ( not plasmid).
o Methicillin resistance is expressed more when incubated at 35° C than at 37° C.
| A | Alteration in ribosomal binding site | |
| B |
Plasmid mediated |
|
| C |
Erythromycin esterase production |
|
| D |
Efflux proteins |
Ans. is ‘None > c’ i.e., Erythromycin esterase production
o All are true.
Mechanism of drug resistance for erythromycin
o Bacterial resistance to erythromycin occurs by:
(i) Target site alteration (alteration in the 505 ribosomal binding site by methylation) by enzyme methylase which is encoded by plasmid -4 Most common
(ii) Altered transport with active efflux to pump it out by efflusx protein —> 2nd most common
(iii) Drug modification by enzyme, i.e. erythromycin esterase rare
o Mechanisms (i) and (ii) are the most common mechanisms for bacterial resistance to erythromycin
o Resistance may be chromosomal mediated or plasmid mediated and it may be inducible or constitutive.
o Resistance to erythromycin implies resistance to all macrolides.
Coming back to question
o Most appropriate answer of this question is None.
o However, if the question is repeated as such go ahead with option ‘c’ because:
1. Two most common mechanism for erythromycin resistance are:
(i) Alteration in ribosomoal binding side (option a) by plasmid encoded (option b) methylase
(ii) Active efflux of drug by efflux protein (option d)
2. Production of erythromycin esterase is an uncommon mechanism for erythromycin resistance.
| A |
Thymidine kinase |
|
| B |
DNA-dependent RNA polymerase |
|
| C |
↓ spectrum |
|
| D |
↓ Side effects |
Ans. is ‘a’ i.e., Thymidine kinase
Both HSV and VZV have been found to develop resistance to acyclovir during therapy the former primarily due to mutants deficient in thymidine kinase activity and the latter primarily by change in specificity of virus directed enzyme so that its affinity for acyclovir is decreased.
Resistance to zidovudine develops due to-
| A |
Mutations at reverse transcriptase |
|
| B |
Increased efflux of the drug from inside the cell |
|
| C |
Increased metabolism of the drug |
|
| D |
Decreased zidovudine 5 triphosphate formation |
Ans. is ‘a’ i.e., Mutations at reverse transcriptase
“Resistance to Zidovudine occurs by point mutation which alters reverse transcriptase enzyme. In the past when AZT was used alone, > 50% patients became nonresponsive to AZT within 1-2 years therapy due to growth of resistant mutants” – KDT
Resistance to Methotrexate develops due to?
| A |
Rapid Cancer cell multiplication |
|
| B |
Deficiency of thymidylate kinase |
|
| C |
Deficiency of thymidylate synthetase |
|
| D |
Increased production of dihydrofolate reductase |
Ans. is ‘d’ i.e., Increased production of dihydrofolate reductase
Methotrexate resistance
- Methotrexate resistance may be due to any of the following mechanism :‑
- Defective transport into cells
- Production of altered form of DHFR that have decreased affinity for methotrexate
- Increased concentrations of intracellular DHFR through gene amplification or altered gene regulation
- Decreased ability to synthesize methotrexate polyglutamates
- Increased expression of a drug efflux transporter, of the MRP (multidrug resistance protein) class
| A | Transformation | |
| B |
Transduction |
|
| C |
Conjugation |
|
| D |
Mutation |
Ans. is ‘d’ i.e., Mutation
Gene responsible for resistance to rifampicin
| A |
Rpo B gene |
|
| B |
Kat G gene |
|
| C |
Rpm B gene |
|
| D |
Emb B gene |
Ans. is ‘a’ i.e., Rpo B gene
| ATT Drug | Gene responsible for drug resistance |
| INH | inhA and Kat G gene |
| Ethambutol | emb B gene |
| Rifampicin | rpoB gene |
| Pyrazinamide |
pncA gene |
| A | The most common mechanism is production of neutralizing enzymes by bacteria | |
| B |
Plasmid mediated resistance is exclusively transferred vertically |
|
| C |
Complete elimination of target is the mechanism by which enterococci develop resistance to vancomycin |
|
| D |
Alteration of target lesions leads to development of resistance to antibiotics in Streptococcus pneumoniae |
Ans. b. Plasmid mediated resistance is exclusively transferred vertically
All are true regarding resistance of penicillin in Staphylococcus aureus, except ‑
| A |
Penicillinase production is transmitted by transduction |
|
| B |
Methicillin resistance is due to change in PBP |
|
| C |
Hospital strains mostly produce type D penicillinase |
|
| D |
Penicillinase production is plasmid mediated |
Ans. is ‘C’ i.e., Hospital strains mostly produce type D penicillinase
Resistance to antibiotics
-
Penicillin resistance is of three types‑
1. Production of beta-lactamase (penicillinase)
-
It inactivates penicillin by splitting beta-lactam ring
-
Its production is controlled by plasmid.
-
Plasmid is transmitted by transduction (mainly) or conjugation.
-
Penicillinase is an inducible enzyme
-
As a result of the widespread dissemination of plasmids containing penicillinase, less than 5% strains of staph. remain susceptible to penicillin.
-
Staphylococci produce four types of penicillinases, A to D. Hospital strains usually form type ‘A’ penicillinase.
2. Changes in bacterial surface receptors by lack or inaccessibility of certain penicillin-binding proteins (PBPs) in the organism.
-
Methicillin-resistant is mainly due to this mechanism and is independent of beta-lactamase production.
-
It is due to the production of PBP 2a.
-
This change ( in bacterial surface receptors) is normally chromosomal.
-
The resistance gene is mec A gene which is a part of a large mobile genetic element – staphylococcal cassette chromosome (SCCmec).
-
This genetic material has been transferred to Staph. aureus from S. seiuri.
3. Development of tolerance to penicillin, by which the bacterium is only inhibited but not killed.
