Embracing the enemy: the diversification of microbial gene repertoires by phage-mediated horizontal gene transfer

doi:10.1016/j.mib.2017.04.010

Current Opinion in Microbiology

Volume 38, August 2017, Pages 66-73

https://doi.org/10.1016/j.mib.2017.04.010 Get rights and content

Highlights

•
Phages drive horizontal gene transfer between prokaryotes.
•
Lysogenic conversion provides novel adaptive traits, at the cost of eventual lysis.
•
Prophages account for a sizeable fraction of bacterial gene repertoires.
•
The environmental rates of specialized and generalized transduction, and their evolutionary relevance, are poorly known.
•
Theoretical work is necessary to understand the role of transduction in the evolution of prokaryotes and in phage therapy.

Bacteriophages and archaeal viruses contribute, through lysogenic conversion or transduction, to the horizontal transfer of genetic material between microbial genomes. Recent genomics, metagenomics, and single cell studies have shown that lysogenic conversion is widespread and provides hosts with adaptive traits often associated with biotic interactions. The quantification of the evolutionary impact of transduction has lagged behind and requires further theoretical and experimental work. Nevertheless, recent studies suggested that generalized transduction plays a role in the transfer of antibiotic resistance genes and in the acquisition of novel genes during intra-specific bacterial competition. The characteristics of transduction and lysogenic conversion complement those of other mechanisms of transfer, and could play a key role in the spread of adaptive genes between communities.

Graphical abstract

Section snippets

Lysogenic conversion

Lysogeny often involves the integration of the temperate phage genome in the host chromosome, even if a growing number of prophages are found to replicate in cells as plasmids [8, 9]. The expression of prophage genes leads to phenotypic changes in the host that may affect many different traits, including virulence, motility, and inter-bacterial competition (see Refs. [5, 10] for reviews). The identification of the determinants of the decision between lysis and lysogeny can thus illuminate the

Specialized transduction

Specialized transduction results from an event of inaccurate excision of the prophage from the chromosome, for example, by ‘illegitimate’ recombination, that leads to the packaging of a section of the prophage and the contiguous chromosomal DNA (Figure 1). Illegitimate recombination depends on the local density of repeats [32], with the consequence that specialized transduction rates may vary widely in function of the chromosomal context of the prophage. Specialized transduction occurs at very

Generalized transduction

Generalized transduction results from errors in discriminating phage from chromosomal DNA during packaging. This mechanism can transfer any chromosomal sequence, including rDNA [38], and its integration in the host chromosome may require homologous recombination. Generalized transduction has been identified in phages packaging their genome using the headful (pac) mechanism [39], one of several packaging systems of dsDNA phages [3]. Mu-like phages systematically transfer a few kilobases of

Determinants of transfer

Many variables affect phage-mediated HGT, and further theoretical work is needed to understand how they could interact in transmission networks (Box 1). The phage host range is a key variable that affects the ability of these processes to spread genes in communities. The analysis of the networks of gene homology between bacteria and phages (so-called transduction networks) suggests that most transfer takes place between closely related taxa [47], in agreement with the traditional view that

Antibiotic resistance

The role of transduction in the spread of antibiotic resistance genes (ARG) is a relatively recent topic of research because these genes are much often identified in conjugative elements than in phages. However, work in this topic is being spurred by several studies that identified ARGs in gut viromes following antibiotic perturbation [58••, 59], and in natural environments [60]. The analysis of viromes is technically challenging because bacterial contamination can be mistaken by transducing

Conclusions

Much remains to be known regarding the role of phages in HGT (Box 2). Even if metagenomics data suggests that generalized transduction may contribute significantly to HGT in prokaryotes, quantitative data on this process is still lacking. Our ignorance is even more dramatic regarding the significance of the contribution of specialized transduction, whose role in prokaryotic evolution remains to be demonstrated. At this stage, the relevance of lysogeny in HGT is well-established, but novel

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

Work in our laboratory is funded by credits from the CNRS and the Pasteur Institute. We thank Mireille Ansaldi, David Bikard, and a reviewer for comments on a previous version of this manuscript, and Louis-Marie Bobay and Aude Bernheim for discussions.

References (75)

B. Koskella
Phage-mediated selection on microbiota of a long-lived host
Curr. Biol.
(2013)
N. Obeng et al.
The significance of mutualistic phages for bacterial ecology and evolution
Trends Microbiol.
(2016)
A.S. Pradeep Ram et al.
Resources drive trade-off between viral lifestyles in the plankton: evidence from freshwater microbial microcosms
Environ. Microbiol.
(2010)
D. Veesler et al.
A common evolutionary origin for tailed-bacteriophage functional modules and bacterial machineries
Microbiol. Mol. Biol. Rev.
(2011)
L. Oliveira et al.
Headful DNA packaging: bacteriophage SPP1 as a model system
Virus Res.
(2013)
T. Kenzaka et al.
High-frequency phage-mediated gene transfer in freshwater environments determined at single-cell level
ISME J.
(2010)
J.A. Gama et al.
Temperate bacterial viruses as double-edged swords in bacterial warfare
PLoS One
(2013)
O. Popa et al.
Phylogenomic networks reveal limited phylogenetic range of lateral gene transfer by transduction
ISME J.
(2016)
F. Enault et al.
Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses
ISME J.
(2017)
F.L. Hellweger et al.
Advancing microbial sciences by individual-based modelling
Nat. Rev. Microbiol.
(2016)

C. Canchaya et al.

Prophage genomics

Microbiol. Mol. Biol. Rev.

(2003)

A. Thierauf et al.

Generalized transduction

Methods Mol. Biol.

(2009)

P.J. Jardine et al.

DNA packaging in double-stranded DNA phages

J.P. Pirnay et al.

The phage therapy paradigm: pret-a-porter or sur-mesure?

Pharm. Res.

(2011)

J. Bondy-Denomy et al.

When a virus is not a parasite: the beneficial effects of prophages on bacterial fitness

J. Microbiol.

(2014)

F. Rohwer et al.

Life in Our Phage World

(2014)

A. Brolund et al.

Plasmidome-analysis of ESBL-producing Escherichia coli using conventional typing and high-throughput sequencing

PLoS One

(2013)

H. Xue et al.

Eco-evolutionary dynamics of episomes among ecologically cohesive bacterial populations

mBio

(2015)

F. St-Pierre et al.

Determination of cell fate selection during phage lambda infection

Proc. Natl. Acad. Sci. U. S. A.

(2008)

L. Zeng et al.

Decision making at a subcellular level determines the outcome of bacteriophage infection

Cell

(2010)

B. Knowles et al.

Lytic to temperate switching of viral communities

Nature

(2016)

C.H. Wigington et al.

Re-examination of the relationship between marine virus and microbial cell abundances

Nat. Microbiol.

(2016)

M. Touchon et al.

Genetic and life-history traits associated with the distribution of prophages in bacteria

ISME J.

(2016)

Z. Erez et al.

Communication between viruses guides lysis–lysogeny decisions

Nature

(2017)

S. Roux et al.

Viral dark matter and virus–host interactions resolved from publicly available microbial genomes

Elife

(2015)

L.-M. Bobay et al.

The adaptation of temperate bacteriophages to their host genomes

Mol. Biol. Evol.

(2013)

C.F. Maurice et al.

Linking the lytic and lysogenic bacteriophage cycles to environmental conditions, host physiology and their variability in coastal lagoons

Environ. Microbiol.

(2013)

J.H. Paul

Prophages in marine bacteria: dangerous molecular time bombs or the key to survival in the seas?

ISME J.

(2008)

M. Asadulghani et al.

The defective prophage pool of Escherichia coli O157: prophage–prophage interactions potentiate horizontal transfer of virulence determinants

PLoS Pathog.

(2009)

R.C. Matos et al.

Enterococcus faecalis prophage dynamics and contributions to pathogenic traits

PLoS Genet.

(2013)

C. Canchaya et al.

Phage as agents of lateral gene transfer

Curr. Opin. Microbiol.

(2003)

L.M. Bobay et al.

Pervasive domestication of defective prophages by bacteria

Proc. Natl. Acad. Sci. U. S. A.

(2014)

S. Lemire et al.

Bacteriophage crosstalk: coordination of prophage induction by trans-acting antirepressors

PLoS Genet.

(2011)

M. De Paepe et al.

Temperate phages acquire DNA from defective prophages by relaxed homologous recombination: the role of Rad52-like recombinases

PLoS Genet.

(2014)

R. Menouni et al.

Bacterial genome remodeling through bacteriophage recombination

FEMS Microbiol. Lett.

(2015)

X. Wang et al.

Cryptic prophages help bacteria cope with adverse environments

Nat. Commun.

(2010)

M. Touchon et al.

The chromosomal accommodation and domestication of mobile genetic elements

Curr. Opin. Microbiol.

(2014)

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Embracing the enemy: the diversification of microbial gene repertoires by phage-mediated horizontal gene transfer

Highlights

Graphical abstract

Section snippets

Lysogenic conversion

Specialized transduction

Generalized transduction

Determinants of transfer

Antibiotic resistance

Conclusions

References and recommended reading

Acknowledgements

Curr. Biol.

Trends Microbiol.

Environ. Microbiol.

Microbiol. Mol. Biol. Rev.

Virus Res.

ISME J.

PLoS One

ISME J.

ISME J.

Nat. Rev. Microbiol.

Prophage genomics

Microbiol. Mol. Biol. Rev.

Generalized transduction

Methods Mol. Biol.

DNA packaging in double-stranded DNA phages

The phage therapy paradigm: pret-a-porter or sur-mesure?

Pharm. Res.

When a virus is not a parasite: the beneficial effects of prophages on bacterial fitness

J. Microbiol.

Life in Our Phage World

Plasmidome-analysis of ESBL-producing Escherichia coli using conventional typing and high-throughput sequencing

PLoS One

Eco-evolutionary dynamics of episomes among ecologically cohesive bacterial populations

mBio

Determination of cell fate selection during phage lambda infection

Proc. Natl. Acad. Sci. U. S. A.

Decision making at a subcellular level determines the outcome of bacteriophage infection

Cell

Lytic to temperate switching of viral communities

Nature

Re-examination of the relationship between marine virus and microbial cell abundances

Nat. Microbiol.

Genetic and life-history traits associated with the distribution of prophages in bacteria

ISME J.

Communication between viruses guides lysis–lysogeny decisions

Nature

Viral dark matter and virus–host interactions resolved from publicly available microbial genomes

Elife

The adaptation of temperate bacteriophages to their host genomes

Mol. Biol. Evol.

Linking the lytic and lysogenic bacteriophage cycles to environmental conditions, host physiology and their variability in coastal lagoons

Environ. Microbiol.

Prophages in marine bacteria: dangerous molecular time bombs or the key to survival in the seas?

ISME J.

The defective prophage pool of Escherichia coli O157: prophage–prophage interactions potentiate horizontal transfer of virulence determinants

PLoS Pathog.

Enterococcus faecalis prophage dynamics and contributions to pathogenic traits

PLoS Genet.

Phage as agents of lateral gene transfer

Curr. Opin. Microbiol.

Pervasive domestication of defective prophages by bacteria

Proc. Natl. Acad. Sci. U. S. A.

Bacteriophage crosstalk: coordination of prophage induction by trans-acting antirepressors

PLoS Genet.

Temperate phages acquire DNA from defective prophages by relaxed homologous recombination: the role of Rad52-like recombinases

PLoS Genet.

Bacterial genome remodeling through bacteriophage recombination

FEMS Microbiol. Lett.

Cryptic prophages help bacteria cope with adverse environments

Nat. Commun.

The chromosomal accommodation and domestication of mobile genetic elements

Curr. Opin. Microbiol.