Antibiotic Resistance in a Hospital Bacterial Population
A hospital ICU tracks a population of Klebsiella bacteria. Before a new carbapenem antibiotic is introduced, 0.01% of bacteria carry a plasmid-borne carbapenemase gene. After six months of heavy carbapenem use, 60% of isolates carry the gene. A clinician argues the antibiotic 'taught the bacteria to make the enzyme' and recommends switching to a different drug class to 'reverse' the resistance. Genetic analysis shows the plasmid also carries genes for resistance to two other drug classes, and the plasmid can transfer between cells by conjugation.
1. Explain why the resistant fraction rose using natural selection, and correct the clinician's 'taught' claim.
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The antibiotic did not teach or induce the enzyme; the resistance gene already existed at low frequency (0.01%). Carbapenem use imposed strong selection: susceptible cells died, while cells carrying the plasmid-borne carbapenemase survived and reproduced. Over six months, the resistant lineage increased to 60%. This is directional selection on pre-existing heritable variation. The 'taught' claim is a Lamarckian error; bacteria do not acquire a new enzyme because of exposure. The variation was present before selection, and selection changed allele frequencies.
2. The plasmid carries resistance to three drug classes and transfers by conjugation. Explain why switching to a different drug class may fail, and what co-selection means here.
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Because the resistance genes are physically linked on the same plasmid, selecting for resistance to one drug co-selects for the others. If the new drug is one of the classes on the plasmid, the population is already largely resistant. Even if the new drug targets a class not on the plasmid, continued use of any drug whose resistance is plasmid-linked maintains the plasmid in the population (co-selection or linkage hitchhiking). Conjugation spreads the plasmid horizontally, so resistance can move to new strains faster than vertical inheritance alone. Switching classes alone is therefore insufficient; the plasmid linkage and horizontal transfer are the key constraints.
3. Predict what happens to the frequency of the carbapenemase gene if carbapenem use is stopped entirely, and explain any caveat.
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In the absence of carbapenems, the resistance gene confers little or no advantage and may carry a fitness cost (plasmid maintenance, enzyme production). Selection would then favor cells without the plasmid, so the frequency of the carbapenemase gene should decline over time. Caveat: if the plasmid also carries resistance to drugs still in use, or if the cost is negligible, the gene may persist. Also, conjugation can maintain the plasmid even without direct selection. So the prediction is a decline, but the linked resistances and horizontal transfer can slow or prevent loss.