Plasmid fitness costs are caused by specific genetic conflicts enabling resolution by compensatory mutation.

James P J Hall,Katie J Muddiman,A Jamie Wood,Steve Paterson,Rosanna C T Wright,Michael A Brockhurst,Ellie Harrison,J Arjan G M De Visser

doi:10.1371/journal.pbio.3001225

James P J Hall, Katie J Muddiman + Show 6 more

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https://doi.org/10.1371/journal.pbio.3001225

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Abstract

Plasmids play an important role in bacterial genome evolution by transferring genes between lineages. Fitness costs associated with plasmid carriage 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 gene expression level. By combining the results of experimental evolution with genetics and transcriptomics, we show here that fitness costs of 2 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 carriage. 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 up-regulating a putative plasmid-borne ParAB operon. The chromosomal mobile genetic element Tn6291, which uses plasmids for transmission, remained up-regulated 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 (HGT) due to their propensity for amelioration by single compensatory mutations, helping to explain why plasmids are so common in bacterial genomes.

Highlights

Plasmid-mediated horizontal gene transfer (HGT) is a powerful force in bacterial evolution
Since prophage induction is a signature of the SOS response, and the P. fluorescens SBW25 lexA homologues PFLU1560 and PFLU3605 were up-regulated by both pQBR57 and pQBR103, we investigated how many of the 16 remaining up-regulated genes were located downstream of a predicted LexA binding site
We show that, rather than emerging from the general bioenergetic demands of replicating DNA, transcribing into mRNA, or translating into protein [20], the majority of the fitness costs of plasmid acquisition come from specific deleterious interactions between plasmid and chromosomal genes

Summary

Introduction

Plasmid-mediated horizontal gene transfer (HGT) is a powerful force in bacterial evolution. Many of the traits necessary for the ecological success of bacteria in new environments are carried between bacterial strains and species by plasmids. Plasmids mobilise antimicrobial resistance genes between pathogens, commensals, and environmental bacteria of diverse species [1,2,3]. Plasmids provide key virulence determinants necessary for colonisation and establishment and factors that assist in immune evasion and pathogen transmission [6,7]. In diverse habitats, plasmids are integral constituents of microbiomes, acting as potent drivers of bacterial evolutionary ecology, in large part through their role as vehicles of HGT [8,9,10,11]

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