Antimicrobial Agents & Resistance - Richardson

Question 1

What is MIC?

Answer 1

Minimum Inhibitory Concentration - Lowest concentration at which bacteria cannot grow

Question 2

What is MBC?

Answer 2

Minimum Bactericidal Concentration - Lowest concentration which causes 1000-fold reduction in bacteria.

Question 3

What is the difference between bacteriostatic and bactericidal antibiotics?

Answer 3

Static = Inhibits growth allowing immune response to clear the infection.

Cidal = Kills bacteria

Question 4

Do antibiotics kill bacteria by generating ROS?

Answer 4

NO.

Question 5

What are the 3 ways bacteria evolve resistance to drugs?

Answer 5

1. Inactivate the drug
2. Alter the drug’s target
3. Alter exposure to the drug

Question 6

Why are gram negative bacteria better at clearing cell-wall antibiotics?

Answer 6

They have a cell membrane and a cell wall allowing them to better efflux. They also can change porins allowing them to not uptake drug. More ways to alter exposure.

Question 7

Why can’t gram positive bacteria alter their exposure to cell-wall antibiotics?

Answer 7

They don’t have an outer membrane protecting their cell wall so they can’t efflux antibiotics or alter uptake via porins. They can only alter target or secrete inactivating enzymes.

Question 8

What is the target of beta-lactam antibiotics?

Answer 8

Trans-peptidases in the bacterial cell wall. This disrupts cell-wall integrity.

Question 9

What links sugars together in bacterial cell walls?

Answer 9

Transglycosylases

Question 10

What are penicillin binding proteins?

Answer 10

Proteins that polymerize and stabilize peptidoglycan of bacterial cell-walls.

Question 11

What is the mechanism of beta-lactams?

Answer 11

B-lactams mimic D-ala-D-ala in peptidoglycans preventing penicillin binding protein from cross-linking peptidoglycan

Question 12

How do beta-lactamases degrade beta-lactams?

Answer 12

Beta-lactamases hydrolyze the same bonds as PBPs allowing bacteria to form peptidoglycan cross-links regardless of drugs.

Question 13

What is alternative way that bacteria can evade B-lactam drugs?

Answer 13

They have PBPs that don’t bind B-lactams but still have transpeptidase activity such as MRSA and N. gonorrhea

Question 14

What did N. gonorrhea evolve to become resistant to penicillin?

Answer 14

1. Mutated porins decreases drug uptake
2. Constitutively expressed efflux pumps
3. Altered PBPs
4. B-lactamases

Question 15

What are the targets of glycopeptide antibiotics?

Answer 15

They cap D-ala-D-ala so that it cannot interact with transpeptidases. Ex. Vancomycin

Question 16

Mechanisms for resistance of glycopeptides such as vancomycin:

Answer 16

Some bacteria can compose their cell walls of D-ala-D-lac cross-links which vancomycin cannot recognize.

Question 17

Which gene encodes resistance to methicillin?

Answer 17

mecA

Question 18

How do bacteria evolve drug resistance before drugs were even invented? Then how is it selected for?

Answer 18

We utilize antibiotics derived from soil bacteria. Pathogenic bacteria can pick up genes via plasmid or phage from other antibiotic-producing soil bacteria and confer resistance. Clinical use of antibiotics has redistributed antibiotic resistance from their natural origin to human pathogens.

Question 19

Three ways bacteria pick up genes?

Answer 19

1. Transformation - Raw DNA (plasmids).
2. Transduction - Infection by phage
3. Conjugation - Pili