Fitness Costs, Co-selection, and Collateral Sensitivity

Why resistance often costs fitness A resistance determinant is an extra burden: a plasmid must be replicated, a pump must be powered, an altered target may work less efficiently. In a drug-free environment the susceptible competitor usually grows faster, so resistant cells are outcompeted. This is why resistance can fall after an antibiotic is withdrawn — but compensatory mutations can restore fitness while keeping the resistance gene, so the decline is often partial and sometimes absent. Co-selection: one drug, several resistances When resistance genes are genetically linked on the same plasmid, transposon, or integron, selecting for one gene selects for all of them. The same happens when a single efflux pump exports two different antibiotics. The practical consequence is that using one antibiotic can maintain resistance to unrelated drugs that are not being used. Collateral sensitivity: the reciprocal trade-off Sometimes evolving resistance to drug A increases susceptibility to drug B. The resistance mechanism — for example, a change in membrane permeability or efflux capacity — can make the cell more vulnerable to a drug it has not encountered. If the trade-off is reliable, alternating or combining drugs could exploit it, but the effect depends on the specific mechanism and drug pair and is not yet a settled clinical rule.