The influence of fluctuating antibiotic exposures and population sizes on the evolution of multidrug resistance

Abstract

Experimental evolution is an important tool used to study the long-term effects of multidrug resistance in bacterial populations. Two major factors that can potentially affect the evolution of resistance are fluctuations in exposures to antibiotics and differences in population sizes. To investigate this, replicate populations of Escherichia coli were subjected to either a single antibiotic or fluctuations between a pair of antibiotics. After these selections, the increase in antibiotic resistance was measured as an increase in MIC, growth rate and carrying capacity compared to the ancestral populations. Contrary to prior expectations, we found that large populations did not show an increase in antibiotic resistance compared to small populations when selected under increasing concentrations of a single antibiotic. Also, large populations showed a lack of costs when exposed to novel antibiotics. When exposed to fluctuations between a pair of antibiotics, large populations were able to evolve a higher resistance than small populations, but again showed a lack of costs in novel antibiotics. These results indicate that there might be a few factors with different levels of influence on large and small populations, such as the presence of resistant subpopulations, upregulation of efflux genes and differences in the distribution of fitness effects. Further experiments are required to clarify the effect of these individual factors.