Drug Resistance and Tolerance

Question 1

Modules upregulated in E. coli persister cells

Answer 1

Toxin-antitoxin modules

Question 2

Describe TA modules

Answer 2

• bicistronic operons widely distributed in the genomes of free-living organisms
• antitoxin is less stable

Question 3

Types of cell death

Answer 3

• apoptosis
• autophagy
• cornification
• necrosis

Question 4

Pathways of apoptosis

Answer 4

• Death-receptor mediated

- mitochondrial mediated

Question 5

Steps in possible model for bacterial cell death

Answer 5

• gyrase inhibition
• superoxide generation
• redox cycling
• Fenton reaction
• Hydroxyl radical damage

Question 6

Describe Fenton chemistry

Answer 6

• Ferrous iron reacts with hydrogen peroxide to produce ferric iron and hydroxyl radical

Question 7

Assumptions for resistance to develop

Answer 7

• exposed bacterium must not die
• resistance must pre-exist antibiotic treatment
  or
• resistance must develop in a protected compartment where antibiotic concentrations are sub-inhibitory
• bacterial numbers must be high

Question 8

Describe a model for the development of resistance during antibiotic exposure

Answer 8

• E. coli and low cipro
• SOS response initiates
• growth of multi-nucleated filaments is interrupted by budding of short progeny cells
• after budding most filaments die but some buds evolve resistance to cipro stress