Evolution of bacterial cross-resistance to lytic phages and albicidin antibiotic

Due to concerns over the global increase of antibiotic-resistant bacteria, alternative antibacterial strategies, such as phage therapy, are increasingly being considered. However, evolution of bacterial resistance to new therapeutics is almost a certainty; indeed, it is possible that resistance to alternative treatments might result in an evolved trade-up such as enhanced antibiotic resistance. Here, we hypothesize that selection for Escherichia coli bacteria to resist phage T6, phage U115, or albicidin will result in a pleiotropic trade-up in the form of cross-resistance, because all three antibacterial agents interact with the Tsx porin. Selection imposed by any one of the antibacterials resulted in cross-resistance to all three of them, in 29 spontaneous bacterial mutants examined in this study. Furthermore, cross-resistance did not cause measurable fitness deficiencies under normal growth conditions for any of the bacterial mutants. A combination of whole-genome and targeted sequenc...