Mechanism of action of antibiotics (Antibacterial agents) Flashcards
How can antibiotics be classified?
Bactericidal, Bacteriastatic, Bacteriolytic
Bactericidal definition
Kill the bacteria
Bacteriostatic definition?
Inhibit or retard bacteria growth and multiplication
Minimum inhibitory concentration defintion?
Lowest concentration of an antimicrobial that will inhibit the visible growth of a micro-organism
Minimum bactericidal concentration?
Lowest concentration fo an anti-microbial required to kill a micro-organism
How can bacteria be classified?
gram staining, aerobic, aerobic
List differences between G+ve and G-ve cells?
+ve have 1 cell membrane with a thick cell wall on the outside made with lots of peptidoglycan
-ve have 2 cell membranes with a thin cell wall in-between made with less peptidoglycan
why is the structure of bacteria important in the mechanism of antibiotics?
Structure of cell wall and membrane is different to humans to can be used as a target for the antimicrobials without damaging host
List 5 mechanisms of action of antibiotics
Inhibit cell wall synthesis Alteration of cell membrane Inhibit protein synthesis Interfere with bacterial nucleic acid Anti-microbial activity - disrupt processes needed for survival of the cell
What makes up the cell wall of the bacteria?
Peptidoglycan
Describe bacterial cell wall synthesis
2 amino sugars make up the peptidoglycan monomer unit (n-acetlyglucosamine and n-acetylmuramic acid)
This unit is transferred across the bacterial cell membrane in a lipid carrier to outside of the cell
Here the chains cross link and form peptidoglycan chain catalysed by penicillin binding protein
List the sites of action of antibiotics acting to inibit cell wall synthesis
Interfere with enzyme catalysing cross linkage - peptidoglycan chain cannot form
Interfere with peptidoglycan monomer
Interfere with lipid carrier do monomer unit cannot cross to the outside of the cell
What is the aim of interfering with formation of cell wall?
Cell lysis
How do beta-lactams work?
Inhibit peptidoglycan synthesis by binding to the penicillin binding protein - so cannot cross-link
How does vancomycin work?
Disrupt peptidoglycan cross-linkage by binding to peptidoglycan monomers
How does bacitracin work?
Disrupt lipid carrier required for glycol transport across the cell membrane
What is the aim of antibiotics targeting the alteration of cell membrane?
Leakage of cell contents due to disruption of cross-membrane potential
How do antibiotics such as polymyxins and daptomycins work (cell membrane)?
Depolarisation of cell and leakage of contents or lysis
At what 2 sites can protein synthesis be inhibited?
30s ribosomes
50s ribosomes
What ribosomal sub unit do aminoglycosides and tetracyclines act?
30s
What ribosomal sub unit do macrolides act?
50s
Describe bacterial protein synthesis?
mRNA attaches to 30s subunit of ribosome
tRNA brings amino acid to 50s subunit
Transpeptidation of amino acid to growing peptide from 50s unit
Ribosome translocates and peptide chain grows, ribosome moves along one codonalong mRNA and new molecules of tRNA attach to 50s
How do tetracylines work?
Inhibit entry of incoming acetyl tRNA
How do aminoglycosides work?
Inhibit the correct reading of mRNA
how do macrolides work?
Inhibit translocation
How does chloramphenicol work?
Inhibits transpeptidation
How do quinolone work?
Inhibit DNA gyrases or topiosomerases that stop supercoiling of DNA
How do metronidazoles work?
Metabolised into toxic metabolites which interfere with DNA - causing inhibitor of DNA replication
How does rifampicin work?
binds to RNA polymerase inhibiting transcription
How do sulphonamides work?
Inhibit folic acid production - inhibiting the production of DNa
How can antibiotics be mis-used?
Incorrect dose
Incorrect duration
Inappropriate choice
Use in warranted situations
What does antibiotic misuse cause?
Resistance
What is MRSa treated with?
Vancomycin
What are 2 classes of antimicrobial resistance?
Natural
Acquired