Mechanisms of Antibiotic Resistance
Concept Name
Antibiotic Resistance
Genetic Loci
blaTEM‑1 (carried on Tn3 transposon) encodes β‑lactamase. mecA (SCCmec cassette in MRSA) encodes PBP2a. vanA (Tn1546 transposon) encodes Vancomycin‑resistant enterococci (VRE) by altering D‑Ala‑D‑Ala to D‑Ala‑D‑Lac.
Intracellular Cascade
Resistance mechanisms: 1) enzymatic inactivation (β‑lactamases, aminoglycoside‑modifying enzymes), 2) altered target (PBP2a in MRSA, mutated DNA gyrase in fluoroquinolone resistance), 3) efflux pumps (MexAB‑OprM in Pseudomonas), 4) reduced permeability (porin mutations).
Required Cofactors
Efflux pumps require ATP or proton motive force. β‑lactamases require zinc (metallo‑β‑lactamases) or serine as active site nucleophile.
Histology Stains
Not applicable; resistance is detected by culture and sensitivity testing (disk diffusion, broth microdilution). PCR for resistance genes (mecA, vanA, blaCTX‑M).
EM Findings
Not applicable for resistance mechanisms, but biofilms (extracellular polymeric substance) are visible on EM and contribute to antibiotic tolerance.
Knockout Phenotype
Deletion of efflux pump genes (acrAB) in E. coli restores susceptibility to multiple antibiotics. Knockout of mecA in MRSA restores methicillin sensitivity.
Specific Toxins
Clavulanic acid (β‑lactamase inhibitor) irreversibly binds serine β‑lactamases. Avibactam is a non‑β‑lactam β‑lactamase inhibitor. Efflux pump inhibitors (PAβN) are experimental.