L15 - Antibacterial chemotherapy II

Question 1

4 recurring themes of antibacterial action?

Answer 1

substrate analogues

steric hindrance

enzyme inactivation

disruption/subversion

Question 2

2 final steps of peptidoglycan synthesis?

Answer 2

transglycosylation

Transpeptidation

Question 3

What are the 2 final steps of PG synthesis catalysed by?

Answer 3

PBPs
bifunctional enzymes
membrane associated

Question 4

2 drug classes that interfere with cell wall biosynthesis?

Answer 4

B-lactams

glycopeptides

Question 5

Drugs in B-lactam class?

Answer 5

penicillins
cephalosporins
carbapenems

Question 6

Drugs in glycopeptide class?

Answer 6

vancomycin

teicoplanin

Question 7

B-lactam mechansism of action

Answer 7

serine residue within active site will break apart 2 D-alaine residues

serin performs nucleophilic attack on B-lactam ring = intemrediate

PBPs are inactivated - irreversible acylation

CROSS LINKING OF PEPTIDE (PEP) SIDE CHAINS BLOCKED

Question 8

What are PG hydrolases?

Answer 8

controlled cleavage of PG for expansion during normal growth

NOT inhibited by B-lactams = weakening of PG especially at DIVISION SITE

Question 9

What does Vancomycin bind to?

Answer 9

D-ala-D-ala

Question 10

Mode of action of vancomycin?

Answer 10

PRIMARILY affects transglycosylation

affects some transpeptidation

Question 11

Is vancomycin active against both gram-ve and gram+ve?

Answer 11

NO

only active gram+ve

Question 12

What is daptomycin?

Answer 12

cyclic lipopeptide

Question 13

Mode of action of daptomycin?

Answer 13

interact with membrane via acyl chain

integrate - Ca2+

aggregation

membrane depolarisation, leakage

Question 14

Mode of action of polymixin B and E (colisitin?

Answer 14

bind to LPS

disrupt IM

flip-flop

Question 15

What are Sulfa drugs (sulfonamides)?

Answer 15

competitively inhibit DHPS

alternate substrate to PABA

create dead end complex instead of dihydropteroate

no tetrahydrofolate

Question 16

Mode of action of trimethoprim?

Answer 16

bind to Dihydrofolate reductase

Dihydrofolic acid not made into tetrahydrofolic acid

Question 17

2 important quinolones?

Answer 17

nalidixic acid

ciprofloxacin

Question 18

What 2 enzymes do quinolones act on?

Answer 18

DNA gyrase
Topo IV

usualyy catalyse ATP-dependent dsDNA breakage/rejoining

Question 19

Mode of action of quinolones?

Answer 19

base stacking interactions between quinolones and 5’ base

no rejoining of DNA molecule

Question 20

Mode of action of rifampicin?

Answer 20

TRANSCRIPTION inhibitor

binds B-subunit of prokaryotic RNApol

interferes with initiation of transcription - ABORTIVE INITIATION (2-3 nt length)

Question 21

Mode of action fo mupirocin?

Answer 21

substrate analogue to inhibit isoleucyl tRNA synthetase

isoleucine cannot bind so cannot be linked to tRNA - NO CHARGING

Question 22

2 oxazolidinones?

Answer 22

Linezolid

Tedizolid

Question 23

Mode of action of oxazolidonones?

Answer 23

Gram+ve only

binds to 50S subunit

interferes with binding/positioning of initiator tRNA in ribosomal P-site

Question 24

What do macrolides consist of?

Answer 24

Macrocyclic lactone ring - amino sugar and another sugar attached

Question 25

Most used macrolide?

Answer 25

azithromycin (15-membered azalide)

Question 26

Macrolide mode of action?

Answer 26

Bind to 23s rRNA at peptide exit site in 50S subunit

block exit of growing peptides in 50S tunnel

premature dissociation of peptidyl-tRNA from P-site

Question 27

Mode of action of fusidic acid?

Answer 27

binds to EFG

which binds to ribosome A-site and moves tRNAs through ribosome using GTP

FA locks EFG onto ribosome and prevents conformation shift needed to dissociate from ribosome