Quorum sensing (QS) is used to regulate the secretion of virulence factors in a multitude of pathogenic bacteria and is therefore considered a potential target for drug development. It is still unclear what type of resistance strategies can evolve to overcome QS inhibition and how would these be affected by the social nature of QS and secreted virulence factors. Here we combined mathematical modeling and experiments with the bacteria P. aeruginosa to show the existence of several types of evolutionary responses that all suppress the effect of a mutation that imitate the administration of QS inhibiting drug. However, these strategies have a very different social outcome when competed with their parental “non-resistant” strain. We show that these differences are attributed to the nature of the benefit they confer and to their ability to induce the quorum response in the parental drug-inhibited strain.
