Displacement of Bacterial Plasmids by Engineered Unilateral Incompatibility

Abstract

Bacterial plasmids employ copy number control systems to ensure that they do not overburden their hosts. Plasmid incompatibility is caused by shared components of copy number control systems, resulting in mutual inhibition of replication. Incompatible plasmids cannot be stably maintained within a host cell. Unilateral incompatibility, in which the plasmid replicons are compatible but one plasmid encodes for the replication inhibitor of the other, leads to rapid displacement of the inhibited plasmid. Thus, we propose that the unilateral incompatibility can be used to eradicate an undesirable plasmid from a population. To investigate this process, we developed deterministic and stochastic models of plasmid dynamics. An analysis of these models provides predictions about the efficacy of plasmid displacement.