MIIM - Antibiotics I - Week 9

Question 1

What is the multiplication threshold for disease and what effect do antibiotics have?

Answer 1

It is the level of microbial multiplication within the body required to cause disease. It usually begins in the later phase of being infected. Antibiotics reduces microbial multiplication to be below the threshold so the disease never occurs (or much less severe symptoms)

Question 2

What are antibiotics (and other drug classes like them) directed at?

Answer 2

Replicating organisms

Question 3

List the four classifications of antibiotics.

Answer 3

Source
Chemical structure
Spectrum
Mechanism of action

Question 4

Name two antibiotics classes that are classified by having a B-lactam ring.

Answer 4

Penicillin
Cephalosporin

Question 5

Name and describe the three key considerations for an antibiotic to be safe and effective in humans (6).

Answer 5

Selective toxicity
-target the organism not humans

Access to the site of infection
-achieve adequate levels where the organism is

Provision of appropriate levels for an appropriate time
-maintain adequate levels to allow inhibition or killing

Question 6

True or false
Organisms that are resistant to an antibiotic at one site in the body may not be resistant at other sites.

Answer 6

True - organisms resistant at one site may be sensitive at other sites

Question 7

List 9 major sites of action that a given antibiotic can have.

Answer 7

Nucleic acid replication
Folic acid
RNA synthesis
Peptide synthesis
Nucleotide synthesis
Mycolic acid synthesis
Nicotinamide (antimycobacterial)
Cell membrane synthesis
Peptidoglycan synthesis

Question 8

Describe how antimicrobial agents enter gram positive and negative bacteria.

Answer 8

Positive - enter easily through the loose outer wall
Negative - must go through narrow porin channels

Question 9

Briefly describe bacterial cell wall synthesis in 5 steps.

Answer 9

Production of the peptidoglycan monomer in the cytoplasm
Transport across the membrane
Cleavage of the existing peptidoglycan by autolysins
Addition of the new monomer
Peptide crosslinking by transpeptidation by transpeptidases

Question 10

What is the mechanism of action for a B-lactam antibiotic? What is it a structural analogue of exactly?

Answer 10

It acts as a structural analogue of D-ala - D-ala. They inhibit transpeptidases as well as enzymes that remodel the cell wall.

Question 11

What are penicillin binding proteins and how do they determine the spectrum a given antibiotic?

Answer 11

Transpeptidases and other enzymes involved in remodelling the cell wall.
Different bacteria may have different kinds of these proteins and will therefore determine the spectrum of the antibiotic

Question 12

Describe the consequence of an antibiotic binding to terminal D-ala - D-ala residues. Give an example of an antibiotic that does this.

Answer 12

Prevents cross-linking and thus prevents the incorporation of additional NAG-NAM subunits into the growing peptidoglycan chain, weakening the cell wall.
Vancomycin

Question 13

Briefly describe how bacitracin antibiotics work.

Answer 13

It acts after the NAG-NAM subunit has been added to the chain.
It prevents dephosphrylation of the phospholipid carrier, preventing its regeneration.

Question 14

What gram type is bacitracin effective against? Considering its mechanism of action, is it significantly toxic to humans or not?

Answer 14

Effective against gram positives and some gram negatives.
Has significant toxicity, so is topical only.

Question 15

What is the consequence of inhibiting cell wall synthesis?

Answer 15

The bacteria continue to grow, the cell wall weakens, and eventually the bacteria lyses.

Question 16

Define a spheroplast and where these can be found.

Answer 16

They are a bacterium bound by its cell membrane and lacking a cell wall. They can be found if bacteria grow in a medium in which cell wall synthesis inhibitors are found.

Question 17

Briefly describe how the cytoplasmic membrane of bacteria can be targetted. What kind of molecules do they act as? What do they interact with and what happens as a result? Are they effective against gram negative bacteria?

Answer 17

The membrane can be targetted by altering its permeability and causing leakage of intracellular components.
They act as cationic detergents.
They are effective against gram negatives.

Question 18

Consider an antibiotic that targets the cytoplasmic membrane. Would they have high or low toxicity?

Answer 18

High toxicity so topical only.

Question 19

Briefly describe the three steps of polypeptide synthesis.

Answer 19

Initiation - mRNA associates with the initiating tRNA on 30S. 50S then binds to the 30S.
Elongation - tRNA sequentially elongate the peptide chain as the mRNA moves through the ribosome.
Termination - occurs when a stop codon is reached.

Question 20

Name four stages of polypeptide synthesis that can be targetted by antibiotics.

Answer 20

Initiation
Peptidyl transfer
Translocation
tRNA synthesis

Question 21

What is the mechanism of action for aminoglycosides (2)?

Answer 21

Inhibits the initiation process by inhibiting the association of mRNA to 30S. This results in the misreading of the mRNA code.

Question 22

Which gram types are aminoglycosides effective against?

Answer 22

Gram negative and positive
(other less toxic antibiotics are more suitable for positive however).

Question 23

Do aminoglycosides have high or low toxicity?

Answer 23

High

Question 24

What are aminoglycosides reserved for?

Answer 24

Serious infections

Question 25

What do tetracyclines bind to and what happens as a result? Are tetracyclines bactericidal or bacteriostatic?

Answer 25

It bins to 30S and prevents tRNA alignment.
Generally bacteriostatic.

Question 26

Do tetracyclines have high or low toxicity?

Answer 26

Low toxicity

Question 27

Are tetracyclines rarely or widely used? What is a consequence of this?

Answer 27

Widely used to resistance is a problem.

Question 28

Briefly describe how chloramphenicol works.

Answer 28

Binds to peptidyl transferase, blocking chain elongation.

Question 29

Is chloramphenicol bactericidal or bacteriostatic?

Answer 29

Bacteriostatic

Question 30

Does chloramphenicol have high or low toxicity?

Answer 30

High

Question 31

What condition can chloramphenicol cause? Is it reversible?

Answer 31

Aplastic anaemia - irreversible

Question 32

Does chloramphenicol have a broad or narrow spectrum? Is it highly effective or not?

Answer 32

Broad spectrum, highly effective

Question 33

Briefly describe how macrolides work.

Answer 33

They bind to 50S, preventing translocation.

Question 34

Are macrolides broad or narrow spectrum?

Answer 34

Broad