The distribution of plasmid fitness effects explains plasmid persistence in bacterial communities

Abstract

Plasmid persistence in bacterial populations is strongly influenced by the fitness effects associated with plasmid carriage. However, plasmid fitness effects in wild-type bacterial hosts remain largely unexplored. In this study, we determined the distribution of fitness effects (DFE) for the major antibiotic resistance plasmid pOXA-48 in wild-type, ecologically compatible enterobacterial isolates from the human gut microbiota. Our results show that although pOXA-48 produced an overall reduction in bacterial fitness, the DFE was dominated by quasi-neutral effects, and beneficial effects were observed in several isolates. Incorporating these data into a simple population dynamics model revealed a new set of conditions for plasmid stability in bacterial communities, with plasmid persistence increasing with bacterial diversity and becoming less dependent on conjugation. Moreover, genomic results showed a link between plasmid fitness effects and bacterial phylogeny, helping to explain pOXA-48 epidemiology. Our results provide a simple and general explanation for plasmid persistence in natural bacterial communities.

Limited and strain-specific transcriptional and growth responses to acquisition of a multidrug resistance plasmid in genetically diverseEscherichia colilineages

“…However, our data are consistent with those of another recent study that tested the fitness effect of a given plasmid across the range of genetic backgrounds present in a host species. Like ours, this study revealed diverse fitness impacts ranging across a continuum from costly to beneficial (Alonso-del Valle et al, 2020). These data highlight that the fitness effects of a plasmid can be highly strain-specific, and thus are likely to arise from specific genetic interactions rather than the generic biosynthetic costs of plasmid maintenance.…”

Collateral sensitivity associated with antibiotic resistance plasmids

“…We performed control experiments mimicking the growth conditions of the competition experiments to ensure that plasmid loss in plasmid-carrying strains is negligible. Moreover, previous results indicated that plasmid conjugation under the experimental conditions used for the competition assays do not significantly affect relative fitness determinations (Alonso-del Valle et al, 2020).…”

“…The clinical E. coli strains used in this study were isolated during the R-GNOSIS project, which included representative ESBL-producing enterobacteria from hospitalized patients in the Ramon y Cajal University Hospital during a 2 year period (Hernández-García et al, 2018b;León-Sampedro et al, 2020). The E. coli strains used here, and their corresponding transconjugants, were described and characterized previously (Alonso-del Valle et al, 2020) and Supplementary file 1D).…”

The ecology of plasmid-coded antibiotic resistance: a basic framework for experimental research and modeling

“…They also used a system of differential equations describing the interactive change of the components population density, antibiotic concentration ( -lactam), nutrient level and Bla concentration ( -lactamase). Valle et al [109] studied the distribution of plasmid fitness effects for the major antibiotic resistance plasmid pOXA-48. They found this to be dominated by quasi-neutral effects, which, incorporated in a simple system of ordinary differential equations, indicated that plasmid stability increases with bacterial diversity and is less dependent on conjugation.…”