Antimicrobial compounds and modes of action - Part 1 Flashcards
What do antimicrobials target?
They target essential biological processes or unique features of microbes
Why must antimicrobial targets be sufficiently different to the host?
To reduce potential off-target activity and side effects (toxicity)
Selective toxicity
What is selective toxicity?
It is the ability of the drug to kill or inhibit pathogen while damaging host as little as possible
What is the difference between broad and narrow spectrum antimicrobials?
Broad affects many different species of organism
Narrow is specific to one particular group (e.g. gram negative bacteria)
What is the difference between antimicrobials and antibiotics?
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
What is minimum inhibitory concentration (MIC)?
Lowest conc of substance that inhibits growth of microbe
What is maximum lethal concentration (MLC)?
Lowest conc of substance that kills microbe
What is the difference between static antimicrobials and cidal antimicrobials?
Static - prevent growth of microbe so immune defence can kill it (e.g. fungistatic)
Cidal - kill microbe directly (e.g. bacteriocidal)
What type of microbe is bacteria?
Prokaryotic
What is the general mechanism of action with antibacterial drugs?
They target essential bacterial processes including synthesis of cell wall, protein synthesis and plasma membrane
What is the major component of bacterial cell walls and what is its purpose?
Peptidoglycan
Provides rigidity and strength
Why is peptidoglycan a good target for antibacterials?
Because it is not found in humans
Describe the structure of peptidoglycan
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
How does inhibition of cell walls affect bacteria cells?
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
What is the mechanism of action for penicillin?
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
What is the mechanism of action for vancomycin?
Which bacteria is vancomycin active against?
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
What type of bacteria is daptomycin active against?
What is the mechanism of action of daptomycin?
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
Name the 3 ways protein synthesis can be prevented
- inhibiting peptide (amide) bond formation
- Inhibit tRNA recruitment
- Inducing mistranslation of mRNA
What is the mechanism of action for erythromycin?
Bacteriostatic
Binds to 50S ribosomal subunit (larger portion) = inhibits aminoacyl translocation
Transfer of tRNA is prevented = stops protein synthesis
Describe the mechanism of action of tetracycline
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
What is the mechanism of action for kanamycin?
Bacteriocidal
Interacts with 30S ribosomal subunit (smaller portion) - inhibits ribosomal translocation and promotes mistranslation of mRNA transcirpts = produces functionally defective proteins.
