ABSTRACT
The process of selection of antibiotic resistance in microorganisms essentially belongs to the category of directional selection. Antibiotic-mediated selection acts as a progressive force that favors genetic variability, leading to the continuous restoration of the fit of bacterial populations confronted with the antibiotic challenge. In most cases, an antibiotic exerts its selective pressure in a gradual way, both at the human individual level (gradients of antibiotic concentrations are formed in the body), and at the human populational level (gradients of antibiotic consumption in the society). Effective directional selection of resistant bacterial populations will occur in these gradually changing antibiotic fields. Gradual environmental change leads to gradual evolutionary change. Under gradual antibiotic pressure, and if the cost of selection is tolerable, low-level resistance may evolve to high-level resistance. As proposed by F.Jacob, adaptation typically progresses through small changes involving a local search in the space of possibilities (Jacob, 1977). In an antibiotic-polluted world, the various bacterial adaptive responses form a field of resistance genotypes, and to each one of them a fitness value can be assigned. That fitness essentially reflects the efficacy (adequacy) of the mechanism of resistance. The distributions of fitness values over the space of resistance genotypes constitute a resistance fitness landscape (Kauffman, 1993). Little hills or hillsides may correspond to low-level mechanisms of resistance; big mountains, to very efficacious high-level mechanisms. Adaptive evolution is frequently a hill-climbing process; to reach
a high peak, successive slopes should be frequently climbed. From the point of view of the surveillance of the process of antibiotic resistance, the emergence of low-level antibiotic resistance should be considered as a signal of alarm, a hallmark of a possible evolutionary trend leading to the heights of therapy-resistant bacterial organisms.
