EVOLVABILITY OF BACTERIA ADAPTING TO ANTIBIOTICS: ESCHERICHIA COLI ACQUIRES INCREASED ADAPTABILITY TO CHLORAMPHENICOL THROUGH GENOMIC AMPLIFICATION

Bacteria can evolve high resistance to antibiotics when grown under continuous selective pressure for only a few days in the lab. This adaptation may advance in several evolutionary paths. While paths involving accumulation of mutations in both target genes and general drug resistance mechanisms has been well characterized, the role of structural changes has received less attention. In particular, it is unknown how early structural changes can dictate adaptive potential. Here, we focus on the evolution of resistance through genomic amplification and find that early transposon translocation facilitates future adaptive amplification of resistance genes. By genotyping multiple clones isolated at different time points during the evolution of resistance to chloramphenicol in a ‘morbidostat’ setting we reveal newly acquired mutations, gradual copy number changes and new genomic junctions. By measuring the evolvability of clones with different genome architecture we identify a duplication step which facilitates adaptation to higher drug concentration in a rapid and highly directional route through amplification. Our results suggest that early genomic changes can dictate future evolutionary paths and that identification of such motifs may enable prediction of adaptive potential.