Key Points
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Owing to their wide ecological distribution and genomic diversity, Pseudomonas spp. and their phages provide an excellent model to study the effect of phage–host interactions either at the single cell level or the population level in diverse environments.
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Phage–host interactions at the single cell level have a role in the struggle between host and phage for control over the cellular resources. To achieve this, bacteria try to prevent phage adsorption or degrade and/or silence foreign DNA, whereas phages look for way to circumvent these defences and redirect host functions to optimize the production of phage progeny.
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In laboratory environments, the selective pressure that is exerted by phages is shown to act as a trigger for host evolution and a factor that influences host, which indicates that phages affect the environmental role of Pseudomonas spp. However, translating these findings to more complex environments remains the major challenge for environmental phage ecologists in the future.
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Phages affect the pathogenicity of Pseudomonas spp., often in an indirect manner, predicting a complex role for phages in shaping the pathogenicity of environmental strains. Deciphering the underlying mechanisms could yield novel strategies to combat pathogenic strains of Pseudomonas and provide key insights into understanding fundamental biological questions contained in the 'viral dark matter'.
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Initial results from clinical trials and patient case studies illustrate the potential safety and efficiency of Pseudomonas phages as tailored antimicrobials against Pseudomonas aeruginosa. Although it remains to be seen whether phage therapy will be made available as a standardized market product, we expect that it will become more widely available as an option to treat problematic infections in a patient-specific manner.
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Phage-derived enzymes and other genetic elements have tremendous biotechnological potential for the development of novel antimicrobials against Gram-negative bacteria (for example, engineered endolysins) and synthetic biology applications.
Abstract
Species in the genus Pseudomonas thrive in a diverse set of ecological niches and include crucial pathogens, such as the human pathogen Pseudomonas aeruginosa and the plant pathogen Pseudomonas syringae. The bacteriophages that infect Pseudomonas spp. mirror the widespread and diverse nature of their hosts. Therefore, Pseudomonas spp. and their phages are an ideal system to study the molecular mechanisms that govern virus–host interactions. Furthermore, phages are principal catalysts of host evolution and diversity, which directly affects the ecological roles of environmental and pathogenic Pseudomonas spp. Understanding these interactions not only provides novel insights into phage biology but also advances the development of phage therapy, phage-derived antimicrobial strategies and innovative biotechnological tools that may be derived from phage–bacteria interactions.
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Acknowledgements
The Laboratory of Gene Technology is supported by a GOA grant 'Phage biosystems' (GOA/15/006) from KU Leuven. J.D.S., K.D-.W. and B.G.B. hold a post-doctoral mandate (PDM) from KU Leuven.
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R.L. serves as a scientific board member to Lysando AG. This company has exclusively licensed patents from KU Leuven.
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FURTHER INFORMATION
Glossary
- Phage carrier state
-
The phage genome is carried as an unstable episome by the host that can segregate asymmetrically between daughter cells. This segregation results in the transient resistance of a subpopulation and ensures the long-term availability of sensitive cells for infection.
- Temperate phages
-
Phages that can undergo either the lytic cycle or a lysogenic cycle, in which they exist as stable plasmids or integrate their genomes into bacterial chromosomes.
- Prophage
-
During lysogeny, the phage genome is either integrated into the bacterial chromosome or maintained as an extrachromosomal plasmid, and this stably present genome is called the prophage.
- Type IV pilus
-
Surface-exposed hair-like filaments that mediate various functions in bacteria, including motility, DNA uptake, protein secretion and adherence to host cells.
- O-antigen
-
The hydrophilic, immunodominant and outermost domain of bacterial lipopolysaccharide that consists of repeated monosaccharide units that are glycosidically linked. The O-antigen forms the basis for the serological classification of Gram-negative bacteria.
- Non-canonical nucleotides
-
Commonly incorporated into phage genomes, these are nucleotides that have been substituted for, or covalently modified from, the standard adenine, guanine, cytosine andthymine.
- CRISPR–Cas system
-
An RNA-guided prokaryotic adaptive immune system that involves the acquisition of a sequence of the invading DNA (the protospacer) and its insertion into the CRISPR array as a spacer (adaptation). This is transcribed and processed to generate CRISPR RNAs (crRNAs; expression), which direct the cleavage of foreign nucleic acids by Cas proteins at sites that are complementary to the spacer sequence (interference). Type I systems are characterized by the use of a complex of Cas proteins, including Cas3, and are further divided on the basis of their combination of Cas genes and operon organization.
- Degradosome
-
A multiprotein complex in gammaproteobacteria that is built around the endoribonuclease RNaseE, which is responsible for the decay of mRNA.
- Metabolomics
-
A collective term for the methods used to determine, on a large-scale, the metabolite levels in biological extracts, including both gas and liquid chromatography-based mass spectrometers.
- Replisome
-
The machinery that is used by the cell to replicate DNA by separating the double helix and then synthesizing a complementary sequence on each strand to form two double-stranded DNA polymers that are faithful copies of the original.
- Divisome
-
A transmembrane multiprotein apparatus that forms mid-cell after replication and segregation of the chromosome, and facilitates cell division.
- Lysogenic conversion
-
Following insertion into the genome, specific prophage elements can induce changes in the phenotype of the infected bacterium.
- 'Arms race' dynamic
-
In this model, selective pressure between a host (Pseudomonas) and its parasite (phage) leads to an increasingly more resistant host population and virulent parasite population, as each species has to constantly evolve to maintain the same level of fitness. Consequently, each generation is better adapted than its ancestor generations in both species.
- Fluctuating selection dynamics
-
A mode of co-evolution that is characterized by fluctuating selection pressures in variable environments. In this instance it leads to phages evolving to infect common bacterial genotypes, providing a benefit to rare host resistance alleles that then become dominant; at which point phages start targeting the new dominant bacteria.
- Lysogen
-
A bacterial cell in which a mobilizing prophage exists in a dormant state, with its host-lethal genes suppressed by a transcriptional repressor.
- Mucoid phenotype
-
Pseudomonas strains that cause persistent infections as they produce excessive amounts of the extracellular polysaccharide alginate that render them resistant to phagocytosis and to antibiotics.
- Endolysin
-
A type of peptidoglycan hydrolase that is encoded by many bacteriophages to weaken the peptidoglycan layer of the host and release phage progeny at the end of the lytic cycle.
- Cryptic prophage
-
An ancestral prophage that no longer has the ability to produce infectious phage progeny following induction.
- Serotype conversion
-
A subset of cells in a species of bacteria that shares the same exposed cell surface antigens. Modifications to these antigens can lead to the conversion to another serotype.
- Synthetic biology
-
The application of design and engineering principles to biological systems to artificially manipulate them for useful purposes.
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De Smet, J., Hendrix, H., Blasdel, B. et al. Pseudomonas predators: understanding and exploiting phage–host interactions. Nat Rev Microbiol 15, 517–530 (2017). https://doi.org/10.1038/nrmicro.2017.61
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DOI: https://doi.org/10.1038/nrmicro.2017.61
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