Antimicrobial Mechanisms 2 Flashcards
What are the features outside of a bacteria cell?
Cell wall and cell membrane
What two monosaccharide units make up the peptidoglycan cell wall?
NAM
NAG
What does transpeptidases do?
Transpeptidase is a membrane-bound enzyme that catalyses peptide cross-linking between two adjacent peptidoglycan cell walls.
What are the features of a gram +ve bacteria cell wall?
Thick
strong
porous
drugs can penetrate to the cell membrane
What are the features of a gram -ve cell wall?
Thin wall
additional outer membrane- provides barrier to cell wall and inner membrane
What is the purpose of a cell wall?
Protect cell membranes from rupture and helps maintain the shape of the cell
What is the ideal bond angle in beta-lactam ring
120 degrees
Process of cell wall synthesis
serine residue on enzyme transpeptidase attacks beta-lactam ring and acylates enzyme, transpeptidase now inactive, which prevents the formation of structural cross-linking in bacterial cell wall, cell weakened, bursts and dies
What do beta-lactamases do
Inactivate the beta lactam ring
What are the aims of drug development for penicillin G
- increase acid stability for oral administration
- increase resistance to beta-lactamases
- increase spectrum of activity
Name two beta-lactamase resistant drugs
amoxycillin
methicillin
What can prevent beta-lactamases from opening the beta-lactam ring but retain binding to transpeptidase
Larger side chains
Isoxazoyl penicillins have good activity against which penicillin resistant infection
Streptococcal aureus
95% of hospitals detected S. aureus strains are now insensitive to which drug
methicillin
Which groups favour inhibition of gram +ve bacteria
Hydrophobic
Which groups favour inhibition of gram -ve bacteria
Hydrophilic (best if group is attached to carbon to carbonyl)
What antibiotic is biosynthesised by the exapndase enzyme?
cephalosporins
cephalosporins have good activity against which type of baterial infections?
Gram negatvie
Fourth generation are…
zwitterionic
What is the benefit of zwitterion in cephalosporins?
enhances ability to cross outer membrane of gram -ve bacteria
carbapenems target which kind of bacteria
broad spectrum
monobactams target gram +ve or gram -ve bacteira?
gram -ve
What is the role of clavulanic acid?
It is an irreversible beta-lactamase inhibitor, it binds to the beta-lactamase active site and inactivates the enzyme which means it cannot open the beta-lactam ring which enhances the effect of antimicrobials.
What class of antibiotic is vancomycin in?
glycopeptide
How does vancomycin work?
forms stable hydrogen bonded dimer
inserts between peptidoglycan, forces peptides away so cannot cross-link
cell bursts and lyses
Which type of bacterial infections is Vancomycin used for?
Gram +ve bacteria only, cannot cross gram -ve cell membrane
Why does vancomycin need to be injected?
does not cross gut membrane
What antibiotic targets the cell membrane?
Gramidicin A
How does gramicidin work?
forms an ion channel across cell wall in gram +ve bacteria
What is gramicidin A used to treat?
used in topical medicines to treat infected wounds e.g. eye drops
