Questions: Antibiotic Resistance Mechanisms

Question 1

MRSA (methicillin-resistant Staphylococcus aureus) resists beta-lactam antibiotics primarily through which mechanism?

• A. Secretion of beta-lactamase enzymes that hydrolyze the antibiotic
• B. Efflux pumps that expel methicillin before it can bind its target
• C. Production of an altered penicillin-binding protein (PBP2a) that methicillin cannot bind effectively
• D. Loss of outer membrane porins that prevent methicillin from entering the cell

Answer: (C)

MRSA carries the mecA gene encoding PBP2a, a modified penicillin-binding protein with low affinity for beta-lactam antibiotics. This is target modification — the antibiotic's binding site is structurally changed so the drug cannot inhibit cell wall synthesis. Beta-lactamase (option A) does exist in other resistant strains but is not the primary MRSA mechanism; efflux pumps and porin loss are characteristic of different organisms like Pseudomonas.

Question 2

Antibiotic resistance in a bacterial population is primarily generated by mutations that arise during treatment, so resistance is a new problem created each time a patient takes antibiotics.

• T. True
• F. False

Answer: False

While spontaneous mutation does contribute to resistance, horizontal gene transfer (HGT) — via conjugation, transformation, or transduction — allows bacteria to acquire pre-existing resistance genes from other cells, including from entirely different species. This means resistance genes that evolved elsewhere can spread rapidly through a population without any new mutation occurring. HGT is why resistance can emerge and spread far faster than mutation rates alone would predict.

Question 3

Explain why stopping an antibiotic course early, once symptoms improve, can accelerate the evolution of antibiotic resistance.

Model answer: Stopping early leaves behind partially resistant bacteria that survived the initial antibiotic exposure. These survivors, enriched for resistance traits, reproduce and become the dominant population. The selective pressure of the incomplete course has effectively culled susceptible bacteria while selecting for the less susceptible ones, producing a more resistant population than existed before treatment began.

This is natural selection in action. At the start of treatment, the bacterial population is mostly susceptible with a small fraction having partial resistance. A full course kills even those partially resistant cells. An early stop allows the partially resistant survivors to proliferate. Symptoms improve when the bulk of the susceptible population is eliminated, but that improvement does not mean the infection is gone — the surviving bacteria are exactly the ones best equipped to resist the drug.