Paper I
Question
Write FOUR mechanisms of antimicrobial resistance in bacteria with examples.
Answer
Four mechanisms of antimicrobial resistance in bacteria, with examples:
- Enzymatic drug inactivation/degradation — the bacterium produces an enzyme that inactivates the antibiotic before it can act; e.g., β-lactamases (including extended-spectrum β-lactamases, ESBLs) hydrolyzing the β-lactam ring of penicillins/cephalosporins, produced by many Gram-negative organisms such as E. coli and Klebsiella pneumoniae.
- Alteration of the drug target site — mutation or modification of the antibiotic’s target molecule reduces drug binding affinity while preserving target function; e.g., altered penicillin-binding proteins (PBP2a) in Methicillin-resistant Staphylococcus aureus (MRSA), or mutated DNA gyrase/topoisomerase IV conferring fluoroquinolone resistance.
- Decreased drug uptake/permeability — reduction or loss of the porin channels/outer membrane proteins that antibiotics use to enter the bacterial cell; e.g., porin loss in Pseudomonas aeruginosa contributing to carbapenem resistance.
- Active efflux of the drug — efflux pump systems actively export the antibiotic out of the bacterial cell before it can reach an effective intracellular concentration; e.g., tetracycline efflux pumps (Tet proteins) in various Gram-negative and Gram-positive bacteria.
(A fifth mechanism sometimes cited: bypass/development of an alternative metabolic pathway — e.g., acquisition of an alternative, drug-insensitive enzyme, as with vancomycin-resistant enterococci acquiring altered peptidoglycan precursors (D-Ala-D-Lac instead of D-Ala-D-Ala), reducing vancomycin binding.)