L16 - Antimicrobial Use, Resistance & Surveillance

Question 1

What are the four main mechanisms of antibiotic resistance?

Answer 1

Inactivation
Altered target/overproduction of target
Reduced accumulation (decreased uptake/increased efflux)
Bypassing of antibiotic sensitive process

Question 2

Define intrinsic resistance

Answer 2

Inherent features of the bacterial species, usually expressed by chromosomal genes

Question 3

Define acquired resistance

Answer 3

Resistant features caused by mutations in chromosomal genes, or acquisitions of plasmids/transposons

Question 4

Define plasmid

Answer 4

Extra-chromosomal genetic elements that replicate independently of the chromosome

Question 5

Define transposon

Answer 5

Mobile genetic elements capable of transferring themselves from one DNA molecule to another
Not capable of independent replication
Recognition seq. at end of transposon for transposases

Question 6

Describe the role of plasmids in resistance

Answer 6

Transferred from cell-cell by conjugation
Carry antibiotic resistant genes
Plasmid may be lost in absence of antibiotic

Question 7

Which plasmids (small/large) are conjugative?

Answer 7

Large plasmids are conjugative

Question 8

Describe the contribution of transposons to antibiotic resistance

Answer 8

Central region of transposon often carries antibiotic resistance genes
Can transpose into plasmids and spread

Question 9

Describe the range of resistance exchange

Answer 9

Between similar organisms

Resistance cannot pass between all organisms directly

Question 10

Describe resistance to Sulphonamides - Chromosomal encoded

Answer 10

Hyperproduction of PABA
Mutation in DHPS
DHPS lowers affinity for sulphonamides

Question 11

Describe resistance to Sulphonamides - Plasmid encoded

Answer 11

Duplication of DHPS enzyme

Binds Sulphonamides 10000x less effectively

Question 12

Describe resistance to Quinolones - gyrA

Answer 12

Chromosomal encoded only
gyrA mutations confer Nalidixic acid resistance
N-terminal mutations in DNA gyrase reduce affinity of binding

Question 13

Describe resistance to Aminoglycosides

Answer 13

Plasmid/transposon encoded

Enzymatic modification of the antibiotic, decreasing uptake

Question 14

What are the three classes of enzymes that confer resistance to Aminoglycosides?

Answer 14

Acetyltransferases (AAC)
Adenyltransferases (AAD)
Phosphotransferases (APH)

Question 15

Describe resistance to Tetracycline

Answer 15

Plasmid/transposon encoded

Membrane proteins mediating energy-dependent efflux

Question 16

Describe resistance to Vancomycin

Answer 16

Inducible/Transposon encoded
Vancomycin binds to D-Ala-D-Ala of murein precursors
Resistant strains synthesise D-Ala-D-Lac

Question 17

Describe resistance to Beta-Lactams

Answer 17

Reductions in permeability (altered porins)
Alteration of target (PBP)
Enzymatic inactivation (beta-lactamse)

Question 18

What strategies are available for counteracting resistance?

Answer 18

Development of new antibiotics
Enzyme inhibitors
Limiting antibiotic use
Reduction in preventable HAIs
Education

Question 19

Describe resistance to Quinolones - gyrB

Answer 19

gyrB mutations confer Nalidix acid + Ciprofloxacin resistance
aa substitutions reduce affinity of binding