Evaluating the effect of horizontal transmission on the stability of plasmids under different selection regimes

In theory, plasmids can only be maintained in a population when the rate of horizontal gene transfer is larger than the combined effect of segregational loss and the decrease of fitness associated with plasmid carriage. Recent advances in genome sequencing have shown, however, that a large fraction of plasmids do not carry the genes necessary for conjugation or mobilization. So, how are so-called non-transmissible plasmids able to persist? In order to address this question, we examined a previously published evolutionary model based on the interaction between P. aeruginosa and the non-transmissible plasmid pNUK73. Both our in silico and in vitro results demonstrated that, although compensatory adaptation can decrease the rate of plasmid decay, the conditions for the maintenance of a non-transmissible plasmid are very stringent if the genes it carries are not beneficial to the bacterial host. This result suggests that apparently non-transmissible plasmids may still experience episodes of horizontal gene transfer occurring at very low frequencies, and that these scattered transmission events are sufficient to stabilize these plasmids. We conclude by discussing different genomic and microbiological approaches that could allow for the detection of these rare transmission events and thus to obtain a reliable estimate of the rate of horizontal gene transfer.