The impact of genetic diversity on gene essentiality within the<i>E. coli</i>species

Rousset, François; Jc, Caballero Domènech; Piastra-Facon, Florence; Fernández-Rodríguez, Jesús; Clermont, Olivier; Denamur, Erick; Ep, Rocha; Bikard, David

doi:10.1101/2020.05.25.114553

Cited by 7 publications

(10 citation statements)

References 74 publications

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“…2A). These results were confirmed in a recent and separate assessment of gene essentiality among a diverse group of E. coli, demonstrating the absence of emrE, yddA, mdtM, and acrF from the core genome (in this instance the core was defined as genes present in 90% of strains examined) (63). Our phylogenetic analysis highlights that these poorly conserved proteins either are isolated from other family members (e.g., EmrE and YddA) or phylogenetically cluster with homologous proteins (e.g., either MdtM and MdfA or AcrF and MdtF) (11,60,64).…”

Section: Evolutionary Origins and Conservation Of Bacterial Drug Efflux Pumpssupporting

confidence: 66%

The Evolutionary Conservation of Escherichia coli Drug Efflux Pumps Supports Physiological Functions

Teelucksingh¹,

Thompson²,

Cox³

2020

J Bacteriol

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Bacteria harness an impressive repertoire of resistance mechanisms to evade the inhibitory action of antibiotics. One such mechanism involves efflux pump-mediated extrusion of drugs from the bacterial cell, which significantly contributes to multidrug resistance. Intriguingly, most drug efflux pumps are chromosomally encoded components of the intrinsic antibiotic resistome. In addition, in terms of xenobiotic detoxification, bacterial efflux systems often exhibit significant levels of functional redundancy. Efflux pumps are also considered to be highly conserved; however, the extent of conservation in many bacterial species has not been reported and the majority of genes that encode efflux pumps appear to be dispensable for growth. These observations, in combination with an increasing body of experimental evidence, imply alternative roles in bacterial physiology. Indeed, the ability of efflux pumps to facilitate antibiotic resistance could be a fortuitous by-product of ancient physiological functions. Using Escherichia coli as a model organism, here we evaluated the evolutionary conservation of drug efflux pumps and we provide phylogenetic analysis of the major efflux families. We show the E. coli drug efflux system has remained relatively stable and the majority (∼80%) of pumps are present in the core proteome. This analysis further supports the importance of drug efflux pumps in E. coli physiology. In this review, we also provide an update on the role of drug efflux pumps in the detoxification of endogenously synthesized substrates and pH homeostasis. Overall, gaining insight into drug efflux pump conservation, common evolutionary ancestors and physiological functions, could enable strategies to combat these intrinsic and ancient elements.

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Section: Evolutionary Origins and Conservation Of Bacterial Drug Efflux Pumpssupporting

confidence: 66%

The Evolutionary Conservation of Escherichia coli Drug Efflux Pumps Supports Physiological Functions

Teelucksingh¹,

Thompson²,

Cox³

2020

J Bacteriol

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“…We recently identified a retron in a P4-like satellite prophage that is responsible for the essentiality of the exodeoxyribonuclease I SbcB in the E. coli strain H120 (36). Retrons are intriguing genetic elements that comprise a reverse-transcriptase (RT) and a multi-copy single-stranded DNA and were recently shown to form tripartite toxin/antitoxin (TA) systems involved in anti-phage defense (7,8,18,37).…”

Section: P4-like Satellite Phages Encode a Hotspot For Bacterial Immumentioning

confidence: 99%

Prophage-encoded hotspots of bacterial immune systems

Rousset

Dowding

Bernheim

et al. 2021

Preprint

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The arms race between bacteria and phages led to the emergence of a variety of genetic systems used by bacteria to defend against viral infection, some of which were repurposed as powerful biotechnological tools. While numerous defense systems have been identified in genomic regions termed defense islands, it is believed that many more remain to be discovered. Here, we show that P2- like prophages and their P4-like satellites have genomic hotspots that represent a significant source of novel anti-phage systems. We validate the defense activity of 14 systems spanning various protein domains and describe PARIS, an abortive infection system triggered by a phage-encoded anti-restriction protein. Immunity hotspots are present across prophages of distant bacterial species, highlighting their biological importance in the competition between bacteria and phages.

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“…Though there are known examples of how the fitness of one gene in a genome is influenced by the presence or absence of other genes, there has been no systematic, large-scale study of how genetic background, in terms of the presence or absence of genes in a genome, influences the fitness effect of an incoming gene (13). Recently, however, it has been shown that the genetic background of a genome has a direct effect on whether or not a gene is essential (39). We have little knowledge of why some lineages encode genes that others do not, and the extent to which the observed encoded genes influence the likelihood of successfully integrating other incoming genes.…”

Section: Discussionmentioning

confidence: 99%

“…We also propose, alongside the role that sharing function plays, that gene mobility could be an additional mechanism behind the formation of these gene-gene relationships. MGEs are a known link to gene essentiality and virulence in E. coli (4; 39; 43), and they have been implicated in driving accessory genome differences in a Listeria monocytogenes pangenome (44). Here, we have demonstrated that they also influence gene co-occurrences by uncovering hub genes and connected components linked to or encoded on MGEs (24; 25; 7; 45; 46; 47; 48; 49).…”

Section: Discussionmentioning

confidence: 99%

Gene-gene relationships in an Escherichia coli accessory genome are linked to function and mobility

Hall

Whelan

Cummins

et al. 2021

Preprint

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The pangenome contains all genes encoded by a species, with the core genome present in all strains and the accessory genome in only a subset. Coincident gene relationships are expected within the accessory genome, where the presence or absence of one gene is influenced by the presence or absence of another. Here, we analysed the accessory genome of an Escherichia coli pangenome consisting of 400 genomes from 20 sequence types to identify genes that display significant co-occurrence or avoidance patterns with one another. We present a complex network of genes that are either found together or that avoid one another more often than would be expected by chance, and show that these relationships vary by lineage. We demonstrate that genes co-occur by function, and that several highly connected gene relationships are linked to mobile genetic elements. We find that genes are more likely to co-occur with, rather than avoid, another gene, suggesting that cooperation is more common than conflict in the accessory genome. This work furthers our understanding of the dynamic nature of prokaryote pangenomes and implicates both function and mobility as drivers of gene relationships.

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The impact of genetic diversity on gene essentiality within theE. colispecies

Cited by 7 publications

References 74 publications

The Evolutionary Conservation of Escherichia coli Drug Efflux Pumps Supports Physiological Functions

The Evolutionary Conservation of Escherichia coli Drug Efflux Pumps Supports Physiological Functions

Prophage-encoded hotspots of bacterial immune systems

Gene-gene relationships in an Escherichia coli accessory genome are linked to function and mobility

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