Antimicrobial compounds and modes of action - Part 1

Question 1

What do antimicrobials target?

Answer 1

They target essential biological processes or unique features of microbes

Question 2

Why must antimicrobial targets be sufficiently different to the host?

Answer 2

To reduce potential off-target activity and side effects (toxicity)

Selective toxicity

Question 3

What is selective toxicity?

Answer 3

It is the ability of the drug to kill or inhibit pathogen while damaging host as little as possible

Question 4

What is the difference between broad and narrow spectrum antimicrobials?

Answer 4

Broad affects many different species of organism

Narrow is specific to one particular group (e.g. gram negative bacteria)

Question 5

What is the difference between antimicrobials and antibiotics?

Answer 5

Antibiotics - natural products produced by microbes that inhibit or kill other microbes (e.g. penicillin)

Antimicrobials - are synthetic formulations.
They are sometimes based on molecular structure of natural products

Question 6

What is minimum inhibitory concentration (MIC)?

Answer 6

Lowest conc of substance that inhibits growth of microbe

Question 7

What is maximum lethal concentration (MLC)?

Answer 7

Lowest conc of substance that kills microbe

Question 8

What is the difference between static antimicrobials and cidal antimicrobials?

Answer 8

Static - prevent growth of microbe so immune defence can kill it (e.g. fungistatic)
Cidal - kill microbe directly (e.g. bacteriocidal)

Question 9

What type of microbe is bacteria?

Answer 9

Prokaryotic

Question 10

What is the general mechanism of action with antibacterial drugs?

Answer 10

They target essential bacterial processes including synthesis of cell wall, protein synthesis and plasma membrane

Question 11

What is the major component of bacterial cell walls and what is its purpose?

Answer 11

Peptidoglycan

Provides rigidity and strength

Question 12

Why is peptidoglycan a good target for antibacterials?

Answer 12

Because it is not found in humans

Question 13

Describe the structure of peptidoglycan

Answer 13

Polymer of alternating sugars - N-acetyl glucosamine (NAG) and N-acetyl muramic acid (NAM).
NAG-NAM sugar polymers are cross-linked by short peptide chains

Question 14

How does inhibition of cell walls affect bacteria cells?

Answer 14

Can inhibit synthesis or cross linking of sugars in cell wall

Only affects actively growing cells

New cell walls are severely weakened

Internal turgor pressure causes cell lysis and death

Question 15

What is the mechanism of action for penicillin?

Answer 15

it inhibits the bacterial transpeptidase enzyme used to crosslink peptidoglycan chains required for cell wall strength and rigidity.

Insufficient cross-linking between NAG/NAM chains weakens bacterial cell wall strength = causes cell lysis

Question 16

What is the mechanism of action for vancomycin?

Which bacteria is vancomycin active against?

Answer 16

Active against gram positive bacteria

Prevents assembly of NAG/NAM polymers by forming hydrogen bonds and prevents polymer cross-linking.

Insufficient NAG/NAM polymerisation and cross-linking severely weakens bacterial cell walls

Question 17

What type of bacteria is daptomycin active against?

What is the mechanism of action of daptomycin?

Answer 17

Gram positive bacteria - bacteriocidal

Inserts into bacterial plasma membrane where it forms pores (oligomerisation). This increases membrane permeability.
Binding to membrane requires phosphatidylglycerol and pore formation induces membranes depolarisation = cell death

Question 18

Name the 3 ways protein synthesis can be prevented

Answer 18

1. inhibiting peptide (amide) bond formation
2. Inhibit tRNA recruitment
3. Inducing mistranslation of mRNA

Question 19

What is the mechanism of action for erythromycin?

Answer 19

Bacteriostatic

Binds to 50S ribosomal subunit (larger portion) = inhibits aminoacyl translocation
Transfer of tRNA is prevented = stops protein synthesis

Question 20

Describe the mechanism of action of tetracycline

Answer 20

Broad spectrum AB

Binds to 30S ribosomal subunit (small portion) preventing recruitment of charged animoacyl-tRNA molecules to acceptor site on ribosome.
Blocking tRNA recruitment prevents the incorporation of new amino acids into the growing peptide chain

Question 21

What is the mechanism of action for kanamycin?

Answer 21

Bacteriocidal

Interacts with 30S ribosomal subunit (smaller portion) - inhibits ribosomal translocation and promotes mistranslation of mRNA transcirpts = produces functionally defective proteins.