FITNESS BENEFITS TO BACTERIA OF CARRYING PROPHAGES AND PROPHAGE-ENCODED ANTIBIOTIC-RESISTANCE GENES PEAK IN DIFFERENT ENVIRONMENTS

Abstract Bacteria can acquire antibiotic resistance genes (ARGs) via prophages, phage genomes integrated into bacterial chromosomes. Such prophages may influence bacterial fitness via increased antibiotic resistance, protection from further phage infection, or by switching to a lytic lifecycle that releases free phages which can infect phage-susceptible competitors. We expect these effects to depend on environmental conditions because of, for example, environment-dependent induction of the lytic lifecycle. However, our understanding of how costs and benefits of prophage-encoded ARGs vary across environments remains limited. Here, by studying prophages with and without ARGs in Escherichia coli , we distinguished between effects of prophages alone and ARGs they carry. In competition with prophage-free strains, fitness benefits from prophages and ARGs peaked in different environments. Prophage carriage was most beneficial in conditions where induction of the lytic lifecycle was common, whereas ARGs were more beneficial in the presence of antibiotics and when prophage induction was lower. Acquisition of prophage-encoded ARGs by competing phage-susceptible strains was most common when prophage induction, and therefore the amount of free phages, was high. Thus, selection on prophages and ARGs varies independently across environments, which is important for predicting the spread of mobile/integrating genetic elements and their role in antibiotic resistance evolution.