Antibiotics II

Question 1

4 mechanism of antibacterial action

Answer 1

Substrate analogues
Steric hindrance
Enzyme inactivation
Disruption/subversion

Question 2

Is an antibacterial agent that is a pro-drug activated in the host or bacterium: selective toxicity

Answer 2

Bacterium

Question 3

Transglycosylation involves

Answer 3

Involves polymerisation of the glycan strands

Question 4

Transpeptidation involves

Answer 4

cross-linking between glycan strands

Question 5

What proteins catalyse the final peptidoglycan reaction

Answer 5

penicillin-binding proteins

Question 6

Are PBPs monofunctional or bifunctional

Answer 6

Bifunctional: transpeptidase and a glycosyltransferase: membrane-associated enzymes

Question 7

What two antibacterial agent classes target the cell-wall biosynthesis

Answer 7

Beta-lactams and glycopeptides

Question 8

Beta lactams bind what proteins

Answer 8

Penicillin binding proteins (PBPs)

Question 9

Give two examples of beta-lactams

Answer 9

Penicillins and cephalosporins

Question 10

Glycopeptides bind what in the final stages of cell wall biosynthesis

Answer 10

Binds substrate

Question 11

Give two examples of glycopeptides

Answer 11

Vancomycin and teicoplanin

Question 12

Penicillin is a structural analogue of what found on the top of peptidoglycan precursors

Answer 12

D-Ala-D-Ala

Question 13

Beta lactam mechanism of action

Answer 13

Beta lactam used as substrate
Key serine residue performs nucleophilic attack on peptide bonds between D-Ala residues
Transpeptidase binding domain is blocked
No cross-linking
No resistance against osmotic pressures

Question 14

Do peptidoglycan hydrolases contribute to killing vai beta-lactams

Answer 14

Yes, they are not inhbited and cleave peptidoglycan in remodelling. Weaken at division furrow

Question 15

What bonds form between vancomycin and D-Ala-D-Ala, does it occlude the molecule from PBP

Answer 15

Hydrogen bonds, yes

Question 16

Does vancomycin aggect transglycosulation or transpeptidation

Answer 16

Effects transglycosylation more than transpeptidation as it can bind to uncrosslinked PG

Question 17

Is vancoymycin active against gram-negative bacteria, why

Answer 17

Only active against Gram-positive bacteria, narrow spectrum as G-ve bacteria have an outer membrane which has, there is a strict weight limit in the porins and so vancomycin can’t enter.

Question 18

Which antibacterial agent targets membrane integrity

Answer 18

Daptomycin

Question 19

Daptomycin MOA

Answer 19

Interaction of DAP with membrane via acyl chain
Integration of DAP mediated by Ca2+ ions
Aggregation
Membrane depolarisation, leakage of contents, death

Question 20

Which antibiotics are like daptomycin but for gram-negative bacteria

Answer 20

Colistin

Question 21

Polymixin B and E (colistin) differences

Answer 21

One residue

Question 22

MOA of polymyxins

Answer 22

Bind LPS (won’t work on G+Ve) and move into inner membrane. Trigger flip-flop of phospholipids. Selectively toxic yet toxic effects in humasn

Question 23

What are the two antibacterial agent classes against nt metabolism

Answer 23

Sulfonamides (first step) and trimethoprim (final step)

Question 24

What molecule derived from GTP is needed for DNA production

Answer 24

Tetrahydrofolate

Question 25

What are sulfa frugs compeitive inhibitors and alternate substrates for

Answer 25

Dihydropteroate synthase (DHPS)

Question 26

Sulfa drugs as an alternate substrate for DHPS lead to the formation of what complex

Answer 26

dead end complex

Question 27

Sulfa drug is similar to the substrate called what for DHPS

Answer 27

PABA

Question 28

Why are sulfa drugs safeish despite impacting the DNA synthesis pathway

Answer 28

We don't produce tetrahydrofolate, we intake it from the diet

Question 29

IS trimethoprim a competitive inhibitor or a substrate alternative

Answer 29

Competitive inhibitor

Question 30

What enzyme does trimethoprim block (we also have this pathway and enzyme)

Answer 30

Dihydrofolate reductase, (FAH2 --> FAH4)

Question 31

Despite humans having dihydrofolate reductase, why is trimethoprim safe to use?

Answer 31

Mammalian enyzymes are way less susceptible

Question 32

Name one quinolone

Answer 32

Nalidixic acid

Question 33

Name a fluroquinolone

Answer 33

Ciprofloxacin

Question 34

What do quinolones act on

Answer 34

Topoisomerases

Question 35

The two related type II topoisomerases catalyse what type of nucleic acid break

Answer 35

dsDNA

Question 36

Dunction of DNA topoisomerase IV

Answer 36

De-links DNA thtrough decatenation, transient DNA break

Question 37

Function of DNA gyrase

Answer 37

Negative supercoiling, pass molecule through itself to fit into cell

Question 38

MOA of quinolones

Answer 38

Topoisomerase (topo IV or gyrase) catalyses dsDNA break, forms intermediate 5' end complex which is recognised by quinolone and DNA can't be used

Question 39

What interactions do quinolones do

Answer 39

Quinolones form base-stacking interactions, electrostatic interaction. Make specific contacts with Topo IV enzymes.

Question 40

Why are quinolones selective against bacteria

Answer 40

We don't have DNA gyrase Our topoisomerases don't have Tyr residue for stability

Question 41

Antivacterial agents targetting transcription, target which enzyme and which subunit

Answer 41

Target RNApol, beta-subunit

Question 42

What is the only transcription factor inhibitor in clinical use for systemic bacterial infections

Answer 42

Rifampicin

Question 43

Where does rifampicin bind

Answer 43

Beta subunit of prokaryotic RNApol

Question 44

What antibiotic is used to treat TB

Answer 44

Rifampicin

Question 45

MOA of rifampicin

Answer 45

Binds mouth of RNA exit channel, steric block, RNA crash and dissociation. Abortive initiation

Question 46

Are most antibacterials targetting protein synthesis bacteriacidal or bacteriostatic

Answer 46

Bacteriostatic

Question 47

Antibacterial drugs targeting protein synthesis (most) act on what organelle

Answer 47

Ribosome

Question 48

Most antibacterials affecting protein synthesis effect what step

Answer 48

Elongation

Question 49

Mupirocin inhibits formation of what, by inhibiting what enzyme

Answer 49

Mupirocin specifically inhibits formation isoleucyl-tRNA by inhibiting its enzyme, isoleucyl-tRNA synthase.

Question 50

MOA of mupirocin

Answer 50

Compeititve inhibitor of isoleucyl-tRNA synthetase (IleS)

Question 51

Why is mupirocin selectively toxic

Answer 51

Our IleS enzyme is less susceptible

Question 52

What is the fully synthetic class of protein synthesis inhibitors in clinical use

Answer 52

Oxazolidinones

Question 53

Oxazolidnones, two examples

Answer 53

Linezolid, tedizolid

Question 54

Are oxazolidnones bacteriostatic?

Answer 54

Yes

Question 55

Why are ozazolidinones only effective against Gram+ve

Answer 55

Removed by efflux in gram-negs

Question 56

Where do oxazolidnones bind

Answer 56

50S ribosomal unit

Question 57

MOA of ozazolidinones

Answer 57

Sterically occluded A site, interferes with initiation step by affect correct positiononing of initiator tRNA in P site

Question 58

Macrolide structure

Answer 58

Macrocyclic lactone ring, one amino acid and two sugards attatched

Question 59

Macrolides (14- and 16- membered compounds) are naturally produced by what genus

Answer 59

Streptomyces

Question 60

15 membered azalides are natural or semo-synthetic

Answer 60

Semi

Question 61

Azithromycin belongs to what class

Answer 61

Macrolide

Question 62

Macrolides are used to treat STIs. Y/N?

Answer 62

Yes

Question 63

Macrolide MOA

Answer 63

Bind 23S rRNA at E site in 50S subunit, block exit, cause premature dissociation of peptidyl-tRNA from P-site

Question 64

Can some proteins escape the macrolide blockage in the exit site

Answer 64

yes

Question 65

MOA of fuscidic acid

Answer 65

Binds elongation factor G (EF-G), locks onto ribosome and occludes A site

Question 66

Why is fuscidic acid selectively toxic

Answer 66

Preferentially accumulated