T7 phage adaptation to two ribosome-binding antibiotics

Bacteriophages provide one of the few hopes for treating infections with drug-resistant bacteria. Rather than replacing antibiotics, however, phages will likely complement treatment for patients already on drugs. A challenge with dual treatment is that antibiotics may inhibit the growth of phages by inhibiting growth of their bacterial hosts, possibly limiting phage efficacy. But might phages be adapted to grow in the drugs? Here, a wildtype T7 was separately adapted to grow on an E. coli K12 in partially-inhibitory concentrations of chloramphenicol (Cm, 2ug/ml) or kanamycin (Kn, 8ug/ml) as well as in a no-drug control. Of the three phage lines separately adapted to each environment: growth rate was elevated over ancestor for all lines, albeit to different degrees, suggesting that pre-adaptation of phages might translate to enhanced treatment success. Yet, all evolved phages improved fitness in both the drug and no-drug environments regardless of their selective environment of evolution, suggesting that a substantial component of selection was merely for better growth. Generalizing this result, a T7 previously adapted to a different E. coli K12 strain without antibiotics also had a significantly higher fitness than the ancestor in all three cellular environments. These data reinforce other work showing that antibiotics inhibit phage growth, but they offer the possibility that phage adaptation for better growth in perhaps any environment – even one lacking drugs – may improve fitness in the presence of drugs.