Antibiotic Resistance

Question 1

What are the 2 types of antibiotic resistance?

Answer 1

Acquired and inherent

Question 2

Describe acquired resistance?

Answer 2

Where a drug which was previously sensitive has gain some genetic material encoding for resistance.

Question 3

Describe inherent resistance?

Answer 3

Inherently resistance antibiotics lack a pathway or target which a drug interacts with, or the drug is able to gain access to the target.

Question 4

Describe the 4 mechanisms bacteria use to become resistance?

Answer 4

• They can produce enzymes that inactivate antimicrobials.
• They can change the drug target so the antibiotic no longer has any effect.
• They can decrease the permeability of the cell to the drug, meaning the concentration required for the drug to be effective is not achieved.
• Bacteria are able to export the drug from inside the cell.

Question 5

Give examples of the 4 mechanism which bacterium use to become resistant?

Answer 5

• producing enzymes: Beta-lactamases.
• Changing drug target: Methylation of the 23S ribosomal subunit resulting in resistance to erythromycin.
• Decreasing cell permeability: Down regulation of porins.
• Exporting the drug from the cell: Pseudomonas producing efflux pumps which are exchanged for porins.

Question 6

List 4 the ways bacteria are able to change their DNA to develop resistance?

Answer 6

• Chromosomal mutation due to selection pressures.
• Acquisition of a mobile piece of DNA such as a plasmid.
• DNA uptake through transformation.
• DNA transfer between bacteria by viruses through transduction.

Question 7

What is vertical gene transfer?

Answer 7

Genetic information passed from parent cell to progeny via binary fission.

Question 8

What is horizontal gene transfer?

Answer 8

Genes transferred other than through traditional reproduction.
This is the primary reason for resistance.

Question 9

What occurs at a higher rate, spontaneous mutation or acquisition of mobile pieces of DNA?

Answer 9

Acquisition of mobile DNA.

Question 10

What is the advantage of treating an infection with 2 drugs that act in different ways?

Answer 10

If a mutations occurs in one drug target the other drug will still kill the organism.

Question 11

What is conjugation?

Answer 11

Requires cell to cell contact between 2 bacteria and they can exchange plasmids.
This is a type of horizontal gene transfer.

Question 12

What are plasmids?

Answer 12

Small peices of circular double stranded DNA.

Question 13

Give examples of the kinds of genetic material that plasmids can carry?

Answer 13

Genes to allow themselves to ..

• replicate.
• move between cells.
• resistance to antibiotics, heavy metals, UV light etc.

Question 14

Why are plasmids advantageous for bacterial antibiotic resistance?

Answer 14

• can replicate independently of the bacterial chromosome.
• can multiply in high numbers.
• have a high rate of cell-to-cell transfer.
• can be picked up by different species.
• can cary resistance to several drugs at once.

Question 15

What is transduction?

Answer 15

where small pieces of DNA are transferred between bacteria by a virus called a bacteriophage.

Question 16

What is transformation?

Answer 16

When some bacteria die, some naked DNA is released to the surrounding environment.
Some bacteria are capable of taking up this naked DNA and inserting it to their chromosome.

Question 17

How can transformation lead to resistance?

Answer 17

If a bacterium takes up the naked DNA and it inserts into a coding region it can result in a change in the protein.
E.g. in penicillin binding protein, if it chages it can still cross-link peptidoglycan precursors to form the cell wall, but has a reduced affinity for beta-lactam antibiotics. This means penicillin will no longer kill the bacteria.

Question 18

What is the downside to the bacteria of acquiring genetic mutations?

Answer 18

Mutations may result in changes to the normal functioning of the bacteria cell.
This may result in a reduced growth rate aka a ‘fitness cost’.
In an environment without a selective pressure the slow growing mutants will be outgrown by the wild-type and will die away.

Question 19

What does MRSA stand for? What does this mean?

Answer 19

Methicillin resistant Staphylococcus aureus.

This measn the strain is resistant to all beta-lactams.

Question 20

What gene encodes MRSA? Where is it situated?

Answer 20

MecA situated in the bacterial chromosome.

Question 21

What does the MRSA gene mutation encode for?

How is this advantageous for the bacteria?

Answer 21

Encodes a variant of the normal penicillin binding protein with a lower affinity for methicillin.

This allows the bacteria to continue to produce the cell wall even in high concentrations of the drug.

Question 22

What is the role of penicillin binding proteins?

Answer 22

Mediate cross-linking in the peptidoglycan which makes up the bacterial cell wall.

Question 23

What are ESBL’s?

Answer 23

Extended spectrum Beta-lactamases.

Enzymes able to hydrolyse the beta-lactam ring.

Question 24

List non-genetic mechanisms of resistance?

Answer 24

• Protected environment e.g. an abscess.
• Resting stage e.g. dormant TB. Due to less susceptibility to cell wall inhibiting agents such a penicillin.
• Presence of a foreign body e.g. biofilms.

Question 25

Why would an abscess be formed?

Answer 25

If body detects an infection it can attempt to isolate the area.

Question 26

Why are biofilms advantageous for bacterial resistance?

Answer 26

• Due to close proximity of bacteria facilitating gene exchanges.
• Channels for diffusion of nutrients are sometimes too small for antibiotics to penetrate.
• At the bottom of a biofilm, bacteria get less nutrients so divide slower, making them less susceptible to cell wall agents.

Question 27

List ways to prevent spread of resistance?

Answer 27

1. use narrow spectrum antibiotics where possible.
2. Use short courses of antibiotics where possible to maintain commensal flora.
3. Reduce meropenem use and reserve it for last line of defence.
4. Reduce use of anti-biotics in the food industry.
5. Use infection control measures such as hand washing, gloves, gowns etc.