Antibiotic Action

Question 1

Modern medicine relies on antibiotics for?

Answer 1

Surgery and transplantation

Prophylaxis and treatment

Dentistry

Question 2

What is selective toxicity?

Answer 2

Infective organism is selectively inhibited without damaging host

Exploits difference in structure and metabolic features

Question 3

Two modes of antibacterial action

Answer 3

Bacteriostatic- cell growth stops

Bactericidal- kills Bacterial cells

Question 4

What is steric hindrance

Answer 4

Interfere with reactions by altering enzyme responsible

Question 5

Modes of antibiotic inhibition?

Answer 5

1) protein synthesis inhibition
2) cell wall biosynthesis inhibition
3) inhibition of nucleotide biosynthesis/folate synthesis

Question 6

2 drug types which attack nucleotide metabolism

Answer 6

Trimethoprims

Sulpha drugs

Both inhibit formation of tetrahydrofolate an essential component of DNA

Question 7

What Antibiotics target microbes

Answer 7

Macrolides
Lincosamides
Streptogramins
Oxazolidinones
Aminoglycosides
Chloramphenicol 

Aminoglycosides
Tetracyclines

50s

30s

Question 8

Describe Mupirocin?

It’s mode of action

Answer 8

Effective against g+ve
Inhibits isoleucine tRNA synthase

Competitive inhibitor

Selective toxicity due to SNP between histidine 581 which is serine or arginine in eukaryotes

Mupirocin binds 8000x more effectively to Bacterial enzymes than isoleucine.

Question 9

Describe Linezolid?

Answer 9

An oxazolidinone
Bacteriostatic
Active against g+ve removed by effluent in g-ve

Binds to 50s ribosome subunit

Interferes with aa-tRNA at acceptor site

Question 10

Describe Tetracycline?

Mode of action

New generation?

Answer 10

Family of naturally occurring and semi synthetic compounds

Core tetracycline structure
Potential to add chemical groups to top of core cyclic rings

Broad spectrum agents

Binds to 16s rRNA of 30s subunit via hydrogen bonding network

Prevent aa-tRNA associating to ribosome

Tigecycline recently developed and solves resistance problem of previous tetracyclines

Question 11

Aminoglycosides mode of action

Answer 11

Binds to 30s only/ and 50s cause conformational change that affects positions of mRNA codon and aa-tRNA
Causing misread proteins hay imbedd into cell membrane causing destabilisation and cell death

Question 12

Aminoglycosides structure is?

Answer 12

3 ring structure
Amino-hexose
Amino-cyclitol
Amino-hexose

Question 13

Macrolides mode of action?

Answer 13

Binds to 23s rRNA at peptide exit site in 50s subunit
Different macrolides bind to different places

Block exit of growing peptides in the 50s subunit tunnel

Causes premature dissociation of the peptidyl-tRNA from P-site

Question 14

Macrolides structure

Answer 14

Macrocyclic lactose ring with two sugars attached

14-16 members ring compounds produced by streptomyces

Azalides 15 ring
Ketolides 14 ring

Question 15

What is azithromycin

Answer 15

An azalide
World most popular antibacterial agent

Deals with H. Influenza
And Moraxella catarrhalis

Question 16

Structure of steptogramins

Mode of action?

Answer 16

Synergistic drug
Comprises of two structurally unrelated molecules group and group b

Binds to 50s subunit

A–> prevents position of peptidyl-tRNA at P site, inhibits bond formation
B–> inactivated peptidyltransferase

Question 17

What is Synercrid

Answer 17

A streptogramins

Composed of Dalfopriatin (A)
And Quinupristin (B)

Both bind to 50s subunit

Question 18

What are Lincosamides?

Answer 18

Not commonly used
Small group of antimicrobials only Clindamycin and lincomycin developed for clinical use

Binds to 50s subunit preventing peptide bond formation

Question 19

Describe Fusidic acid

Answer 19

Steroid like antibiotic

Interferes with release of Ef-G from ribosome
Is and accessory protein needed for ribosomal translocation
Moves ribosome via ratchet mechanism

Recognises EF-G in bound state
Retains EF-G at bound state in A site
Fusidic acid binds to hinge are of EF-G

Question 20

Which classes of Antibiotics target final stages of cell wall synthesis?

Answer 20

Beta-lactams

• penicillin
• cephalosporins

Glycopeptides

• Vancomycin
• Teicoplanin

Question 21

Mode of action of beta lactams

Answer 21

Structural analogues for D-ala-D-ala

Compete for binding to PBPs

Undergo nucleophilic attack by the PBPs to lead to irreversible acetylation b-lactam so permanently bind to PBPs

Are bactericidal
Cross linking of peptides is blocked

Question 22

What are Beta-lactamases

Answer 22

Enzymes that can confer resistance to B-lactams

4 classes
A, C, D are serine lactamases
B are Metallica-enzymes-use zincions

Evolutionary related to transpeptidase

Question 23

How to protect against beta-lactamases

Answer 23

Serine lactamases inactivated by Clavulanic acid

Question 24

What is vancomycin?

Mode of action?

Answer 24

Interferes with transglycosylation

Doesn’t bind to PBP buns to stem peptide D-ala-D-ala

Large molecule

Forms hydrogen bond with with D-ala-D-ala thus causing steric hindrance

Vancomycin binds to lipid 2 on the outside of the inner membrane this stops cross linking of peptidoglycans and incorporation into wall
Inactive against gram-ve as to large

Question 25

What is Fosfomycin?

Answer 25

Antibiotic rather small
Natural product- 3 ring episode
Bactericidal

Acts on first step of PG synthesis
Binds covalently to essential cysteine residue at active site of MurA

Question 26

Cycloserine?

Answer 26

Small broad spectrum agent

Structural analogy to D-alanine

Competitive inhibitor of alanine race made and D-alanyl-D-alanyl ligase