Antimicrobials and resistance
Đã giới thiệu| English | Ý nghĩa |
|---|---|
| selective toxicity | selective toxicity |
| penicillin-binding protein | penicillin-binding protein |
| horizontal gene transfer | horizontal gene transfer |
Four targets, one rule
- Selective toxicity needs a target human cells lack: the wall (β-lactams → penicillin-binding proteins), the ribosome (30S/50S vs our 40S/60S), DNA enzymes (gyrase, RNA polymerase), folate synthesis (bacteria make it; we import it) ✓.
Report: β-lactamase positive, susceptible to flucloxacillin — the enzyme OPENS the β-lactam ring (hydrolysis), while an altered target (PBP2a) is what defines true methicillin resistance ✓.
{exercise:uni-med0806-targets} {exercise:uni-med0806-mrsa}
Anti-folate drugs are selectively toxic because —
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Each target class exploits a bacterial-vs-human difference: wall, 30S/50S ribosomes, gyrase/polymerase, folate synthesis.
True methicillin resistance (PBP2a) differs from beta-lactamase resistance because PBP2a is —
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Beta-lactamase hydrolyses the drug; PBP2a is the target reshaped so the drug cannot bind - different mechanisms, different reports.
Resistance is arithmetic
- Mutation supplies resistance at ~$10^{-7}$–$10^{-9}$ per cell per generation; an overnight culture (~$10^{9}$ cells per mL) carries mutants against any single drug ✓.
- Two independent hits multiply to ~$10^{-14}$–$10^{-18}$ — why combinations exist; plasmids then move the wins between species (horizontal gene transfer).
{exercise:uni-med0806-resist}
Resistance mutations arise at about 10^-7 to 10^-9 per cell per generation, so an overnight culture —
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10^9-10^10 cells times 10^-7-10^-9 means every culture contains resistant mutants; two independent hits (~10^-14-10^-18) are why combinations exist.