Mechanism of aquiring resistance
- Vertical transmission (daughters acquire trait)
- Horizontal transmission (sisters transfer trait between one another)
Horizontal transmission can be via
- Transformation: a bacterium is lysed \(\to\) nucleic acids released into environment \(\to\) taken up via sister cells
- Conjugation: two sisters form a sex philus (a cytoplasmic bridge) and pass plasmids between themselves
- Transuduction: a phage transfers bacterial nucleic acids accidentally
Mechanism of resistance itself
- Intrinsic resistance (cell lacks drug target, or drug cannot penetrate the cell outer membrane / cell wall)
- Modification of the drug target reduces affinity (e.g. modification of penicillin-binding protein or ribosomal proteins)
- Drug efflux pumps reduce intracellular drug concentration
- Drug destruction by enzymes (e.g. \(\beta\)-lactamase)
- Impaired movement of drug to target site (e.g. loss of porins in the outer membrane of gram negative bacteria \(\to\) prevents cell wall synthesis inhibitors accessing cell wall, or biofilm formation by pseudomonas)
- Increased production of a resource to overcome enzyme blockade (e.g. increased PABA to overcome sulfonamide inhibition of dihydrofolate synthesis)