Antibiotic Resistance Mechanisms

Question 1

How is resistance to B-lactam based antibiotics achieved?

Answer 1

Beta-lactamases.
Limited spectrum: TEM-1, TEM-2.
Extended spectrum beta lactamases: CTX-M, NDM-1

Also simple mutations in the structure of the PBPs can occur.

Question 2

Why are Gram negative bacteria more efficient in their use of B-lactamases?

Answer 2

They have an outer cell wall so the release of BLs into the periplasmic space is sufficient to counteract any antibiotics. Gram positive simply release vast quantities into the space surrounding them, a waste of resources.

Question 3

How can we combat beta lactamases?

Answer 3

Beta-lactamase inhibitors like clavulonic acid, sulbactam, tazobactam.

Question 4

How does Methicillin resistance occur?

Answer 4

Mutation of PBP:

PBP2 –> PBP2a

Question 5

How does resistance to vancomycin typically occur?

Answer 5

Alterations to the target site. D-ala-D-ala –> D-ala-D-lactate.
5H-bonds between D-ala and Vanc = stable inhibitory complex.
4H-bonds between D-lactate and Vanc = unstable inhibitory complex.

Question 6

CTX-M and NDM-1 are what form of B-lactamase?

Answer 6

Extended spectrum beta lactamases (ESBL)

Question 7

How does resistance to sulphonamides occur?

Answer 7

Plasmid encoded dihyropterate synthetase enzyme has reduced affinity for the sulphonamides.

Question 8

Which enzyme can undergo mutation and thus have reduced affinity for trimethoprim?

Answer 8

Dihydrofolate reductase.

Question 9

Drug inactivation features prominently in resistance to which class of drugs?

Answer 9

Aminoglycosides:
Acetylase enzymes add acetyl groups.
Adenylase enzymes add AMP groups.
Adenylylase phosphorylase adds phosphate groups to AMP groups.

Question 10

Beta-lactamase inhibitors:

Answer 10

Clavulonic acid, sulbactam, tazobactam.

Question 11

A mutation in the PBP2 causes what?

Answer 11

Methicillin resistance. PBP2 —> PBP2a, MRSA.

Question 12

Why are aminoglycosides commonly inactivated?

Answer 12

Structure allows for it:
Acetylase enzymes add acetyl groups.
Adenylase enzymes add AMP groups.
Adenylylase phosphorylase adds phosphate groups to AMP groups.

Question 13

TEM-1 and TEM-2 are examples of what?

Answer 13

Limited spectrum Beta lactamases.

Question 14

Sulbactam

Answer 14

Beta-lactamase inhibitors like clavulonic acid, sulbactam, tazobactam.

Question 15

Resistance due drug efflux features prominently for which classes of antibiotics?

Answer 15

Tetracyclines

Quinolones.

Question 16

How does multi-drug resistance often occur?

Answer 16

MDR-efflux pumps.

Question 17

How are tetracyclines and quinolones commonly resisted?

Answer 17

Drug efflux.

Question 18

Tazobactam

Answer 18

Beta-lactamase inhibitors like clavulonic acid, sulbactam, tazobactam.

Question 19

AcrAB/TolC is what?

Answer 19

MDR-efflux pump in E. coli

Question 20

MexAB/OprM is what?

Answer 20

MDR-efflux pump in P. aeruginosa

Question 21

Clavulonic acid

Answer 21

Beta-lactamase inhibitors like clavulonic acid, sulbactam, tazobactam.

Question 22

QAC pump is what?

Answer 22

MDR-efflux pump on S. aureus.

Question 23

How does bacitracin resistance occur?

Answer 23

Increased activity of phosphokinase leading to increased carrier molecules.

Question 24

How does resistance to macrolides occur?

Answer 24

Altered target site.
Plasmid-mediated methylation of 23S rRNA by erm gene.
Inducible or constitutive.

Question 25

The erm gene contributes to resistance to which antibiotic class?

Answer 25

Macrolides.