Piggybacking on Niche Adaptation Improves the Maintenance of Multidrug-Resistance Plasmids

Kloos, Julia Maria; Gama, João Alves; Hegstad, Joachim; Samuelsen, Ørjan; Johnsen, Pål Jarle

doi:10.1093/molbev/msab091

Cited by 34 publications

(32 citation statements)

References 85 publications

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“…As a consequence, small mutations—in some cases just single base changes—can be sufficient to ameliorate even a very large plasmid with hundreds of genes. Previous studies have tended to focus on smaller, nonconjugative replicons [ 25 , 30 , 67 ], or have identified plasmid compensatory mutations with substantial pleiotropic effects: disruption or deletion of conjugative machinery from the plasmid (rendering it immobile) [ 28 , 68 ]; deletion of large portions of the plasmid [ 34 , 69 ]; or disruption of extensive and multifunctional regulatory circuits [ 31 , 33 , 70 ]. In contrast, our data show that single mutations can enable large, natural, conjugative, plasmids to become rapidly accommodated with few obvious trade-offs, and furthermore begins to describe the molecular negotiation by which this occurs ( Fig 9 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Previous studies have tended to focus on smaller, non-conjugative replicons [25,30,64], or have identified plasmid compensatory mutations with substantial pleiotropic effects: disruption or deletion of conjugative machinery from the plasmid (rendering it immobile) [28,65]; deletion of large portions of the plasmid [34,66]; or disruption of extensive and multi-functional regulatory circuits [31,33,67]. In contrast, our data shows that single mutations can enable large, natural, conjugative, plasmids to become rapidly accommodated with few obvious tradeoffs, and furthermore describes the molecular negotiation by which this occurs (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…We show that PFLU4242 expression is induced by a global regulator of secondary metabolism, the GacA/S two-component system, and so our data is consistent with the hypothesis that disruption to GacA/S could exert its effect through repression of PFLU4242. It is possible that global regulators have been implicated in plasmid persistance due to their regulatory effects on more proximal causes of plasmid conflict [31,67]. The combined size of the gacA and gacS genes (~3.4 kb) is over twice that of PFLU4242 (~1.6 kb) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Plasmid fitness costs are caused by specific genetic conflicts

Hall

Wright

Harrison

et al. 2021

Preprint

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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.

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“…It was thought that ARGs would impose a fitness cost, and thus at antimicrobial concentrations below the MSC-resistant bacteria carrying the ARG would be outcompeted by non-resistant bacteria. However, recent evidence suggests that several ARGs may impose a low fitness cost, be cost free (sometimes involving development of compensatory mechanisms), or in some cases confer a fitness benefit (Andersson and Hughes, 2010;Li et al, 2020;Kloos et al, 2021;Pietsch et al, 2021). Consequently, ARBs may persist within microbial communities for a duration related to the fitness cost of AMR and general ability to compete with other microorganisms, in some cases decreasing over time and in others persisting, or actually increasing, even in the absence of antimicrobial selection (Li et al, 2020;Perrin-Guyomard et al, 2020;Kloos et al, 2021).…”

Section: 4mentioning

confidence: 99%

“…However, recent evidence suggests that several ARGs may impose a low fitness cost, be cost free (sometimes involving development of compensatory mechanisms), or in some cases confer a fitness benefit (Andersson and Hughes, 2010;Li et al, 2020;Kloos et al, 2021;Pietsch et al, 2021). Consequently, ARBs may persist within microbial communities for a duration related to the fitness cost of AMR and general ability to compete with other microorganisms, in some cases decreasing over time and in others persisting, or actually increasing, even in the absence of antimicrobial selection (Li et al, 2020;Perrin-Guyomard et al, 2020;Kloos et al, 2021). The interaction of environmental antimicrobial residues and microbial communities will not be dealt with in detail in this scientific opinion.…”

Section: 4mentioning

confidence: 99%

Role played by the environment in the emergence and spread of antimicrobial resistance (AMR) through the food chain

Koutsoumanis¹,

Allende²,

Álvarez‐Ordóñez³

et al. 2021

EFS2

117

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The role of food-producing environments in the emergence and spread of antimicrobial resistance (AMR) in EU plant-based food production, terrestrial animals (poultry, cattle and pigs) and aquaculture was assessed. Among the various sources and transmission routes identified, fertilisers of faecal origin, irrigation and surface water for plant-based food and water for aquaculture were considered of major importance. For terrestrial animal production, potential sources consist of feed, humans, water, air/dust, soil, wildlife, rodents, arthropods and equipment. Among those, evidence was found for introduction with feed and humans, for the other sources, the importance could not be assessed. Several ARB of highest priority for public health, such as carbapenem or extended-spectrum cephalosporin and/or fluoroquinolone-resistant Enterobacterales (including Salmonella enterica), fluoroquinolone-resistant Campylobacter spp., methicillin-resistant Staphylococcus aureus and glycopeptide-resistant Enterococcus faecium and E. faecalis were identified. Among highest priority ARGs bla CTX-M , bla VIM , bla NDM , bla OXA-48like , bla OXA-23 , mcr, armA, vanA, cfr and optrA were reported. These highest priority bacteria and genes were identified in different sources, at primary and post-harvest level, particularly faeces/manure, soil and water. For all sectors, reducing the occurrence of faecal microbial contamination of fertilisers, water, feed and the production environment and minimising persistence/recycling of ARB within animal production facilities is a priority. Proper implementation of good hygiene practices, biosecurity and food safety management systems is very important. Potential AMR-specific interventions are in the early stages of development. Many data gaps relating to sources and relevance of transmission routes, diversity of ARB and ARGs, effectiveness of mitigation measures were identified. Representative epidemiological and attribution studies on AMR and its effective control in food production environments at EU level, linked to One Health and environmental initiatives, are urgently required.

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Piggybacking on Niche Adaptation Improves the Maintenance of Multidrug-Resistance Plasmids

Cited by 34 publications

References 85 publications

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

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

Plasmid fitness costs are caused by specific genetic conflicts

Role played by the environment in the emergence and spread of antimicrobial resistance (AMR) through the food chain

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