Antibiotics 2 Flashcards
What is the structure of peptidoglycan?
Backbone of N-acetyl glucosamine and N-acetyl muramic acid with a peptide chain coming off the muramic acid and a pentapeptide bridge linking the 3rd residue to the 4th residue of the peptide chain
What are the amino acids of the peptide chain in staph aureus?
L-ala, D-glu, L-lys, D-ala
What does the alternating pattern of D and L residues give the peptidoglycan?
rigidity
How is peptidoglycan synthesised?
The precursors are synthesised in the cytoplasm then transported to the inner aspect of the plasma membrane where synthesis continues - when building block is complete it is transported to the outermembrane where cross linking occurs
What is the structure of the building block of the peptidoglycan?
glucosamine and muramic acid bound to a phospholipid, peptide chain with an additional 5th reside of D-ala and the pentaglycine
What happens in cross linking of peptidoglycan?
The 5th glycine in the pentapeptide bridge knocks off the terminal D-ala and binds to the subterminal D-ala
What enzymes cause cross linking of peptidoglycan?
Transpeptidases (penicllin binding proteins)
What is the action of vancomycin?
Binds to terminal D-ala and prevents cross linking of peptidoglycan
Which type of bacteria do vancomycin act against?
Gram positive bacteria (can’t get through outer membrane of gram negative bacteria)
Why are enterococci resistant to vancomycin?
Because they use a D-lax instead of a terminal D-ala
How are vancomycin intermediate resistant staph aureus resistant to vancomycin?
They make extra peptidoglycan to ‘soak up’ vancomycin
What is the action of beta lactams?
Blocks the action of the enzyme for cross linking peptidoglycan. This happens because the beta lactam ring is chemical similar to the D-ala D-ala bond - the enzyme binds to beta lactam instead and this binding deactivates the enzyme
Is beta lactam bactericidal or bacteriostatic?
Bactericidal because the bacteria recognises that its cell wall isn’t being built properly and produce enzymes to break down their own cell wall and effectively commits suicide
What is beta lactamase?
An enzyme in bacteria to act against beta lactam - binds to beta lactam ring and hydrolyses it to make it inactive
What are the two kinds of beta lactamases?
Ones encoded on plasmids (e.g. staph aureus) or ones encoded on chromosomes (e.g. pesudomonas)
What are altered penicillin-binding proteins?
A bacteria mechanism for avoiding beta lactams - use a PBP that beta-lactam can’t bind to e.g. in MRSA (gene is mecA)
Why does antibacterial spectrum of beta lactam antibiotics vary?
- Because different bacteria produce 5-6 different PBP and one particular beta lactam will target only certain PBPs - the more PBPs it binds the bigger its spectrum
- because the access of the antibiotic to the PBP varies due to different solubility
- because the susceptibility to beta-lactamase varies
What is the action of clavulanic acid?
A beta lactam that inhibits plasmid beta lactamase - on binding beta lactamase it will inhibit the action of beta lactamase and also its own action
What is co-amoxyclav?
A combination of clavulanic acid and amoxycillin. Clavulanic acid to inhibit the beta lactamase and amoxycillin to target the PBPs without the threat of beta lactamase.
What is the action of ticarcillin?
To treat pseudomonas - inhibits chromosomal beta lactamase
Why would you require a combination of ticarcillin and clavulanic acid?
If the pseudomonas had a plasmid with beta lactamase - therefore containing both types of beta lactamase
In what ways can antibiotics act on protein synthesis?
recognition, peptidyl transfer, translocation, isoleucyl-tRNA synthesis, formation of initial complex
What is the action of aminoglycosides?
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