FIGURE 3.

Alleviation of the costs of antibiotic resistance by compensatory mutations. (A) A drug susceptible genotype (open circle) experiences an antimicrobial resistance (AMR) mutation (closed circle), which reduces its fitness in the absence of antibiotic. Wild-type fitness is given by the dotted line. (B) A drug susceptible genotype (open circle) experiences an AMR mutation (closed circle), which reduces its fitness in the absence of antibiotic. This genotype subsequently sustains a compensatory mutation which restores fitness but does not eliminate resistance (close triangle). Here, a compensatory mutation arises after the costly AMR mutation. While the compensatory mutation is here depicted as neutral, such mutations may impose a fitness cost on the drug sensitive background (Schrag et al., 1997; Brandis et al., 2012). (C) Compensatory mutations that do not themselves carry a cost may also precede the AMR mutation. Here, a drug susceptible genotype experiences a mutation (open triangle) that does not affect fitness, but which later alleviates the fitness deficit that would have been imposed by the AMR mutation (closed triangle).