AMR

Question 1

How does antibiotic resistance happen?

Answer 1

1. large populations of bacteria proliferate and mutate, some of which will be drug resistant
2. Antibiotics will kill the sensitive types but resistant bacteria will remain and contiue to proliferate, becoming dominant
3. Antibiotic resistance is transferred to other bacteria, compounding the problem

Question 2

How is antibiotic resistance transferred?

Answer 2

There are three main mechanisms:
1. Transduction; bacteriophages mediate transfer of DNA between bacteria via transduction whereby DNA from a bacteria is packaged in a virus and trasferred to another bacteria during infection
2. Transformation; some bacteria are able to take up free DNA from the environment and incorporate e.g. Cholera
3. Conjugation; a sex pilus forms between two bacterias through which plasmid is transferred

Question 3

What are the mechanisms of antibiotic resistance?

Answer 3

Similar mechanisms to drug resistance; drug degredation, increased transport (efflux pumps), decreased uptake, target overexpression, loss or alteration

Question 4

What determines the emergence of antibiotic resistance?

Answer 4

There are several factors including population size, mutation rate, selection pressures and fitness trade-offs

Question 5

How does Mtb go from drug-sensitive to XDR-TB?

Answer 5

In Mtb there are no resistance plasmids or horizontal gene transfer so resistance is acquired as a result of inadequate treatment, poor adherence, PK variability and variable drug penentration. Resistance is then transmitted between humans.

Question 6

What is the role of compensatory mechanisms in AMR?

Answer 6

Rifampicin is a first line treatment for Mtb that binds to RNA polymerase to inhibit transcription. Mtb has evolved a compensatory mechanism via a mutation in rpoB which is a beta subunt of RNA polymerase. Normally changing a highly conserved protein would be expected to have a fitness cost, however looking at clinical isolates its seen that there are no costs.

Question 7

How does antibiotic resistance spread?

Answer 7

this can be spread not only between humans due to overprescription of antibiotics, poor adherance and transmission in healthcare settings but also is impacted by animal health as agriculture uses a lot of antibiotics with resistant strains reaching human populations through fecal contamination or poorly cooked meat where bacteria remains

Question 8

What are drug tolerant persisters?