Antibiotic Resistance Increases Evolvability and Maximizes Opportunities Across Fitness Landscapes

Abstract

Antibiotic resistance continues to grow as a public health problem. One of the reasons for this continued growth is that resistance to antibiotics is strongly selected for in the presence of antibiotics and weakly selected against after their removal. This is frequently thought to be due to the effects of compensatory mutations. However, compensatory mutations are often not found in clinically relevant strains of antibiotic resistant pathogens. Here, we conduct experiments in vitro that highlight the role that fine scale differences in environment play in the maintenance of populations after selection for resistance. We show that differences in the mode of growth, dictated by environmental factors, are capable of reliably changing the force and direction of selection. Our results show that antibiotic resistance can increase evolvability in environments if conditions for selection exist, selecting differentially for newly arising variation and moving populations to previously unavailable adaptive peaks.\n\nSignificanceAntibiotic resistant bacteria are a large and growing problem for public health. A major question has been why antibiotic resistant strains do not disappear when they must compete with higher fitness drug sensitive strains. Here we show that selection for antibiotic resistant strains is particularly sensitive to differences in environmental conditions and that these differences help to define the fitness landscapes upon which these populations adapt. The result is an increase in evolvability, with many adaptive peaks that drug resistant populations can explore through natural selection, making predictions of evolution difficult and selection against resistant strains improbable.