Plasmid fitness costs are caused by specific genetic conflicts

Abstract

Plasmids play an important role in bacterial genome evolution by transferring genes between lineages. Fitness costs associated with plasmid acquisition are expected to be a barrier to gene exchange, but the causes of plasmid fitness costs are poorly understood. Single compensatory mutations are often sufficient to completely ameliorate plasmid fitness costs, suggesting that such costs are caused by specific genetic conflicts rather than generic properties of plasmids, such as their size, metabolic burden, or expression level. Here we show -- using a combination of experimental evolution, reverse genetics, and transcriptomics -- that fitness costs of two divergent large plasmids in Pseudomonas fluorescens are caused by inducing maladaptive expression of a chromosomal tailocin toxin operon. Mutations in single genes unrelated to the toxin operon, and located on either the chromosome or the plasmid, ameliorated the disruption associated with plasmid acquisition. We identify one of these compensatory loci, the chromosomal gene PFLU4242, as the key mediator of the fitness costs of both plasmids, with the other compensatory loci either reducing expression of this gene or mitigating its deleterious effects by upregulating a putative plasmid-borne ParAB operon. The chromosomal mobile genetic element Tn6291, which uses plasmids for transmission, remained upregulated even in compensated strains, suggesting that mobile genetic elements communicate through pathways independent of general physiological disruption. Plasmid fitness costs caused by specific genetic conflicts are unlikely to act as a long-term barrier to horizontal gene transfer due to their propensity for amelioration by single compensatory mutations, explaining why plasmids are so common in bacterial genomes.

A tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among Shigella

“…And since the epidemiological fate of these plasmids had already been documented with regard to azithromycin resistance carried on these plasmids [26], our objective was to investigate the potential other factors that helped shape the observed epidemiological outcome of these plasmids beyond the fact that pKSR100 carried more AMR genes and conferred more AMR phenotypes. The spread and persistence of plasmids may depend on several plasmid and host associated factors such as the plasmid type, host range, conjugative capacity and fitness cost as well as the environments they are in [47][48][49][50][51][52]. Understanding the contributions of each of these factors is important in determining the fate of AMR plasmids found in clinical settings and predicting evolutionary trajectories of those plasmids [17].…”

Ecological and evolutionary solutions to the plasmid paradox

“…The targets of compensatory mutations are often associated with the SOS response, and in particular helicase genes have acquired compensatory mutation across several host-plasmid pairs [57, [60][61][62]. In addition, genes that interact deleteriously with incoming plasmids are often themselves horizontally acquired accessory genes already present in the chromosome [61,68,69].…”

Why are rhizobial symbiosis genes mobile?

“…These costs can often be unpredictable, e.g. owing to interactions between incoming plasmids and MGEs already resident in the genome [ 83 ]. Over time, however, the cost of plasmid acquisition is likely to be resolved through compensatory mutations [ 84 ].…”