Pseudomonas predators: understanding and exploiting phage–host interactions

Smet, Jeroen De; Hendrix, Hanne; Blasdel, Bob; Danis-Wlodarczyk, Katarzyna; Lavigne, Rob

doi:10.1038/nrmicro.2017.61

Cited by 181 publications

(164 citation statements)

References 170 publications

(185 reference statements)

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“…Phages represent the most abundant biological entities on earth, and are key ecological drivers of microbial community dynamics, activity and adaptation; thereby impacting environmental nutrient cycles, agricultural output, and human and animal health [1][2][3][4][5][6][7][8]. Despite nearly a century of pioneering molecular work, the mechanistic insights into phage specificity for a given host, infection pathways, and the breadth of bacterial responses to different phages have largely focused on a handful of individual bacterium-phage systems [9][10][11][12][13]. Bacterial sensitivity/resistance to phages is typically characterized using phenotypic methods such as cross-infection patterns against a panel of phages [14][15][16][17][18][19][20][21][22][23][24][25][26][27] or by whole-genome sequencing of phage-resistant mutants [28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

High-throughput mapping of the phage resistance landscape inE. coli

Mutalik¹,

Adler²,

Rishi³

et al. 2020

Preprint

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Bacteriophages (phages) are critical players in the dynamics and function of microbial communities and drive processes as diverse as global biogeochemical cycles and human health. Phages tend to be predators finely tuned to attack specific hosts, even down to the strain level, which in turn defend themselves using an array of mechanisms. However, to date, efforts to rapidly and comprehensively identify bacterial host factors important in phage infection and resistance have yet to be fully realized. Here, we globally map the host genetic determinants involved in resistance to 14 phylogenetically diverse double-stranded DNA phages using two model Escherichia coli strains (K-12 and BL21) with known sequence divergence to demonstrate strain-specific differences. Using genome-wide loss-of-function and gain-of-function genetic technologies, we are able to confirm previously described phage receptors as well as uncover a number of previously unknown host factors that confer resistance to one or more of these phages. We uncover differences in resistance factors that strongly align with the susceptibility of K-12 and BL21 to specific phage. We also identify both phage specific mechanisms, such as the unexpected role of cyclic-di-GMP in host sensitivity to phage N4, and more generic defenses, such as the overproduction of colanic acid capsular polysaccharide that defends against a wide array of phages. Our results indicate that host responses to phages can occur via diverse cellular mechanisms. Our systematic and highthroughput genetic workflow to characterize phage-host interaction determinants can be extended to diverse bacteria to generate datasets that allow predictive models of how phagemediated selection will shape bacterial phenotype and evolution. The results of this study and future efforts to map the phage resistance landscape will lead to new insights into the coevolution of hosts and their phage, which can ultimately be used to design better phage therapeutic treatments and tools for precision microbiome engineering.3 Introduction:

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Section: Introductionmentioning

confidence: 99%

High-throughput mapping of the phage resistance landscape inE. coli

Mutalik¹,

Adler²,

Rishi³

et al. 2020

Preprint

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“…Experiments to remove these prophage-like sequences revealed remarkable changes in host physiological traits (Zeng et al, 2016;Argov et al, 2017;De Smet et al, 2017). These records of interactions between the genomic parasite and its host may encode valuable ecological information (see Box 3).…”

Section: A Symbio-centric Ecological Speciation Frameworkmentioning

confidence: 99%

Bacterial Diversification in the Light of the Interactions with Phages: The Genetic Symbionts and Their Role in Ecological Speciation

et al. 2018

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Phages have a major impact on microbial populations. In this work, we discuss how predation, transduction, lysogeny, and phage domestication lead to symbio-centric genomic interactions between bacteria and phages, ranging from antagonistic to mutualistic. Furthermore, these interactions influence bacterial diversification and ecotype formation. We then propose an additional consideration in the form of a symbio-centric ecological speciation framework for bacteria. Our framework builds upon classical morphological and molecular taxonomy by also considering bacteria and their phages as a unit of evolutionary selection. This framework acknowledges the considerable effect that phage interaction has on bacterial genomic content, regulation, and evolution, and will advance our understanding of bacterial evolution.

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“…A common theme by which phages affect host physiology to benefit phage progeny development is through the modulation or inhibition of bacterial cellular processes (1,2). Previous studies (6)(7)(8)(9) revealed that SPO1 infection results in the remodelling of several host processes by six (Gp38, Gp39, Gp40, Gp44, Gp50 and Gp51) of the twenty-six genes encoded by the host takeover module.…”

Section: Discussionmentioning

confidence: 99%

“…Much like eukaryotic and archaeal viruses, which derail the host's cellular processes to facilitate viral replication, phages have evolved complex strategies to acquire their bacterial hosts. In order to successfully infect and replicate in the bacterial cell, many phages encode proteins that specifically interfere with essential biological processes of the host bacterium, including transcription, translation, DNA replication and cell division (1). Phage proteins that interfere with host processes are typically small in size (on average ~160 amino acid residues) and are usually produced at high levels early in the infection cycle (2).…”

Section: /Bodymentioning

confidence: 99%

Xenogeneic regulation of the ClpCP protease ofBacillus subtilisby a phage-encoded adaptor-like protein

Mulvenna

Hantke

Burchell

et al. 2019

Preprint

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SPO1 phage infection of Bacillus subtilis results in a comprehensive remodelling of processes leading to conversion of the bacterial cell into a factory for phage progeny production. A cluster of 26 genes in the SPO1 genome, called the host takeover module, encodes for potentially cytotoxic proteins for the specific shut down of various host processes including transcription, DNA synthesis and cell division. However, the properties and bacterial targets of many genes of the SPO1 host takeover module remain elusive. Through a systematic analysis of gene products encoded by the SPO1 host takeover module we identified eight gene products which attenuated B. subtilis growth. Out of the eight gene products that attenuated bacterial growth, a 25 kDa protein, called Gp53, was shown to interact with the AAA+ chaperone protein ClpC of the ClpCP protease of B. subtilis. Results reveal that Gp53 functions like a phage encoded adaptor protein and thereby appears to alter the substrate specificity of the ClpCP protease to modulate the proteome of the infected cell to benefit efficient SPO1 phage progeny development. It seems that Gp53 represents a novel strategy used by phages to acquire their bacterial prey.Significance statementViruses of bacteria (phages) represent the most abundant living entities on the planet, and many aspects of our fundamental knowledge of phage–bacteria relationships remain elusive. Many phages encode specialised small proteins, which modulate essential physiological processes in bacteria in order to convert the bacterial cell into a ‘factory’ for phage progeny production – ultimately leading to the demise of the bacterial cell. We describe the identification of several antibacterial proteins produced by a prototypical phage that infects Bacillus subtilis and describe how one such protein subverts the protein control system of its host to benefit phage progeny development. The results have broad implications for our understanding of phage–bacteria relationships and the therapeutic application of phages and their gene products.

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Pseudomonas predators: understanding and exploiting phage–host interactions

Cited by 181 publications

References 170 publications

High-throughput mapping of the phage resistance landscape inE. coli

High-throughput mapping of the phage resistance landscape inE. coli

Bacterial Diversification in the Light of the Interactions with Phages: The Genetic Symbionts and Their Role in Ecological Speciation

Xenogeneic regulation of the ClpCP protease ofBacillus subtilisby a phage-encoded adaptor-like protein

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