Postsegregational killing does not increase plasmid stability but acts to mediate the exclusion of competing plasmids.

Postsegregational killing (PSK) systems consist of a tightly linked toxin-antitoxin pair. Antitoxin must be continually produced to prevent the longer lived toxin from killing the cell. PSK systems on plasmids are widely believed to benefit the plasmid by ensuring its stable vertical inheritance. However, experimental tests of this "stability" hypothesis were not consistent with its predictions. We suggest an alternative hypothesis to explain the evolution of PSK: that PSK systems have been selected through benefiting host plasmids in environments where plasmids must compete during horizontal reproduction. In this "competition" hypothesis, success of PSK systems is a consequence of plasmid-plasmid competition, rather than from an adaptive plasmid-host relationship. In support of this hypothesis, a plasmid-encoded parDE PSK system mediated the exclusion of an isogenic DeltaparDE plasmid. An understanding of how PSK systems influence plasmid success may provide insight into the evolution of other determinants (e.g., antibiotic resistance and virulence) also rendering a cell potentially dependent on an otherwise dispensable plasmid.