Speaker
Johannes Cairns
Description
Historical contingency has been shown to affect drug resistance
evolutionary trajectories. However, the extent of this effect has been
unclear. Here we address this by exposing E. coli to 24 equivalent drug
histories, consisting of one drug-free and three drug-containing epochs,
only altering the order of exposure. We further repeat the experiment
by introducing the T4 bacteriophage, since bacteriophages are
increasingly being used to treat bacterial infections alongside
antibiotics. We find dramatic differences between histories in resistance
evolutionary patterns, with outcomes ranging from virtually no
resistance to virtually complete multidrug and phage resistance. We
also identify factors responsible for desirable and poor outcomes. For
instance, the presence of bacteriophage almost invariably results in a
strong reduction in antibiotic resistance. These results show that
historical contingency directs drug resistance trajectories to highly
variable outcomes with predictable patterns that could be exploited in
therapy optimization
Primary author
Johannes Cairns
