Antibiotic resistance and sustainable healthcare

Question 1

Antibiotic resistance

Answer 1

Bacteria are no longer killed or inhibited by antibiotic drugs

Question 2

Antimicrobial resistance

Answer 2

Microorganisms are no longer killed/inhibited by antimicrobials

Question 3

How does antibiotic resistance happen?

Answer 3

Antibiotics kill bacteria causing the illness as well as good bacteria
The bacteria that are drug-resistant are allowed to grow and takeover
They reproduce and form anew generation of resistant bacteria

Question 4

Intrinsic resistance

Answer 4

Bacteria are naturally resistant due to enzymes that deactivate drug or reduced drug uptake

Question 5

Methods of acquired resistance

Answer 5

Can be via mutation of horizontal gene transfer

Question 6

How do mutations lead to antibiotic resistance?

Answer 6

Antibiotics act as an environmental stressor
This activates an SOS pathway (down regulation of DNA repair mechanisms)
Increased ROS leads to increased frequency of mutations and therefore increased errors in protein synthesis
This new generation is resistant

Question 7

What is vertical gene transfer?

Answer 7

Genes pass from parents to next generation

Question 8

What is horizontal gene transfer?

Answer 8

Bacteria picks up genes from the environment to incorporate into its own genome in one of three ways:
Transformation: donor cell releases DNA into the environment. Competent cells pick up DNA and incorporate into own genome
Transduction: phage infect bacterial cell and integrate into host genome. When they move into the lytic phase they infect a new host and take some of the original host’s DNA into the new cell
Conjugation: donor cell contains plasmids and plasmid moves to new cell via pilus

Question 9

Direct selection

Answer 9

Bacterium exposed to antibiotic A and then resistant to antibiotic A

Question 10

indirect co-selection

Answer 10

Bacterium exposed to antibiotic A but becomes resistant to A, B, C etc

Question 11

Cross resistance

Answer 11

some bacteria naturally resistant due to efflux pumps in cell wall. Exposure of bacteria to antibiotic A causes antibiotic A, B and C to be pumped out so the bacteria cell will survive

Question 12

Co-resistance

Answer 12

genetic linkage of multiple resistance genes. On a plasmid, you may have two genes for resistance to two antibiotics. Only need to expose bacterial cell to one of those antibiotics in order for the entire plasmid to be selected for and maintained

Question 13

Conjugation

Answer 13

• Transfer of plasmids bearing resistance mechanisms

- Tra(nsfer) genes for conjugation by building pilus

Question 14

Gram +ve bacteria

Answer 14

Thick peptidocglycan but no outer membrane - more permeable to antibiotics
MRSA

Question 15

Characteristics of MRSA

Answer 15

• Facultative anaerobic bacteria
• Methicillin resistant
• Opportunistic pathogen - catheters, diabetes sufferers etc
• Resistance mediated by range of mobile genetic elements e.g. SCCmec element

Question 16

B-lactam

Answer 16

• B-lactam antibiotics bind PBPs preventing cell wall synthesis
• B-lactams have low affinity for PBP2a - no effect on cell wall synthesis

Question 17

ESBL resistance

Answer 17

Cleave B-lactam class of antibiotics but still susceptible to carba-penams

Question 18

Carbapenam resistance

Answer 18

Last resort, resistance via carbapenemases

Question 19

How to incentivise antibiotic development

Answer 19

• More funds for early stage research
• De-link profit from sales with subsidies for industry
• Global antibiotic development fund
• Harmonise global regulation to streamline approval

Question 20

Phage therapy

Answer 20

Bacteriophage infect bacteria
During lytic cycle, they lyse bacteria and kill them
Bacteria can still develop phage resistance