Mechanisms of Antibiotic Resistance
One-Sentence Definition
The biochemical strategies bacteria use to neutralize antibiotics: destroy the drug, change the target, keep the drug out, pump it out, or bypass the pathway.
Simple Explanation
Five ways to survive a drug — break it, disguise the target, lock the door, throw it back out, or use a different route.
Detailed Scientific Explanation
| Strategy | How it works | Classic examples |
|---|---|---|
| Enzymatic inactivation | Hydrolyse or modify the drug | β-lactamases (ESBL, AmpC, Carbapenemases: KPC, NDM, OXA-48); aminoglycoside-modifying enzymes |
| Target modification | Alter the binding site | mecA → PBP2a (MRSA); vanA → D-Ala-D-Lac (VRE); lipid A remodeling (Colistin Resistance); gyrA/parC (fluoroquinolones); rpoB (rifampicin); ribosomal methylation (erm, macrolides) |
| Reduced permeability | Lose or downregulate porins | OprD loss in Pseudomonas aeruginosa (carbapenems); porin loss in Klebsiella pneumoniae |
| Active efflux | Pump the drug out | Efflux Pumps — AcrAB-TolC, MexAB-OprM |
| Target bypass / overproduction | Use an alternative enzyme or make more target | dfr (trimethoprim), sul (sulfonamides), thymidine auxotrophy |
| Protection of the target | Shield without altering it | qnr (quinolones), tet(M) ribosomal protection |
Combinations matter. Carbapenem resistance in K. pneumoniae often needs both an enzyme and porin loss; single mechanisms give borderline MICs that are the hardest for both labs and prediction models.
Mechanism
Genes arrive by Horizontal Gene Transfer on Plasmids, integrons, and transposons, or mechanisms arise by Mutation and Selection in chromosomal genes and their regulators.
Clinical Importance
- Determines which agents remain usable and whether combination therapy is required
- Some mechanisms predict cross-resistance beyond the tested drug
Research Importance
- β-lactamase inhibitor design; structural rationale via Structural Bioinformatics
Diagnostic Relevance
- Phenotypic clues (e.g., inducible clindamycin resistance, D-test) and molecular assays for specific genes
AMR Relevance
This note is the mechanistic core of Antimicrobial Resistance.
Related MOCs
Active Recall Questions
- Name the five broad resistance strategies.
- Which two mechanisms combine to give carbapenem resistance in Klebsiella?
- Why is mecA an example of target modification rather than enzymatic inactivation?