FIG 4.

Fitness landscapes in antibiotic resistance. At the top is an image of the classic fitness landscape metaphor developed in 1932 by Sewall Wright, where in a bidimensional plane (black) different genotypes are represented, their corresponding height in the vertical axis showing the fitness of each genotype (reproductive success) under the conditions of the landscape. Red ovals correspond to the variation (for instance, mutation) from one genotype to another one (yellow lines). Note that series of mutations (pathways) might reach low (C), medium (D), or high (A and B) fitness peaks (for instance, reaching very high MICs), but some of these pathways might have originated just by random drift (without natural selection) in the flat area of the landscape. If this landscape is crumpled as a paper ball (bottom left), peaks can go into proximity, and the genotype selected into a peak can have access to other fitness peaks (eventually resulting in genetic recombination or exchange). At the bottom right, the paper ball is deployed to illustrate the fitness landscape.