Antibiotic Resistance Mechanisms Flashcards
How is resistance to B-lactam based antibiotics achieved?
Beta-lactamases.
Limited spectrum: TEM-1, TEM-2.
Extended spectrum beta lactamases: CTX-M, NDM-1
Also simple mutations in the structure of the PBPs can occur.
Why are Gram negative bacteria more efficient in their use of B-lactamases?
They have an outer cell wall so the release of BLs into the periplasmic space is sufficient to counteract any antibiotics. Gram positive simply release vast quantities into the space surrounding them, a waste of resources.
How can we combat beta lactamases?
Beta-lactamase inhibitors like clavulonic acid, sulbactam, tazobactam.
How does Methicillin resistance occur?
Mutation of PBP:
PBP2 –> PBP2a
How does resistance to vancomycin typically occur?
Alterations to the target site. D-ala-D-ala –> D-ala-D-lactate.
5H-bonds between D-ala and Vanc = stable inhibitory complex.
4H-bonds between D-lactate and Vanc = unstable inhibitory complex.
CTX-M and NDM-1 are what form of B-lactamase?
Extended spectrum beta lactamases (ESBL)
How does resistance to sulphonamides occur?
Plasmid encoded dihyropterate synthetase enzyme has reduced affinity for the sulphonamides.
Which enzyme can undergo mutation and thus have reduced affinity for trimethoprim?
Dihydrofolate reductase.
Drug inactivation features prominently in resistance to which class of drugs?
Aminoglycosides:
Acetylase enzymes add acetyl groups.
Adenylase enzymes add AMP groups.
Adenylylase phosphorylase adds phosphate groups to AMP groups.
Beta-lactamase inhibitors:
Clavulonic acid, sulbactam, tazobactam.
A mutation in the PBP2 causes what?
Methicillin resistance. PBP2 —> PBP2a, MRSA.
Why are aminoglycosides commonly inactivated?
Structure allows for it:
Acetylase enzymes add acetyl groups.
Adenylase enzymes add AMP groups.
Adenylylase phosphorylase adds phosphate groups to AMP groups.
TEM-1 and TEM-2 are examples of what?
Limited spectrum Beta lactamases.
Sulbactam
Beta-lactamase inhibitors like clavulonic acid, sulbactam, tazobactam.
Resistance due drug efflux features prominently for which classes of antibiotics?
Tetracyclines
Quinolones.