Epistatic interactions can lower the cost of resistance to multiple consumers

It is widely assumed that resistance to consumers (e.g., predators or patho gens) comes at a "cost," that is, when the consumer is absent the resistant organisms are less fit than their susceptible counterparts. It is unclear what factors determine this cost. We demonstrate that epistasis between gen es that confer resistance to two different consumers can alter the cost of resistance. We used as a model system the bacterium Escherichia coli and tw o different viruses (bacteriophages), T4 and lambda, that prey upon E. coil . Epistasis tended to reduce the costs of multiple resistance in this syste m. However, the extent of cost savings and its statistical significance dep ended on the environment in which fitness was measured, whether the null hy pothesis for gene interaction was additive or multiplicative, and subtle di fferences among mutations that conferred the same resistance phenotype.