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Potential phage therapy virus massively alters RNA metabolism during infection

Next-Generation approaches detail bacteriophage life cycle as it replicates inside P. aeruginosa



IMAGE: This is a picture of the bacteriophage life cycle. view more

Credit: Anne Chevallereau and colleagues

Using metabolomic and transcriptomic analyses, a research group led by Rob Lavigne of the University of Leuven in Belgium and Laurent Debarbieux of the Institut Pasteur in France reveals that a bacteriophage that infects the opportunistic bacterium Pseudomonas aeruginosa, metabolizes host RNA to replicate itself inside the cell. The findings are published on July 5, 2016 in PLOS Genetics.

Phage therapy, which aims to use naturally occurring viruses to treat bacterial infections, is often touted as a potential alternative to antibiotic treatment, but little is known about phage lifecycles, outside of a few model species. Using a bacteriophage that infects P. aeruginosa, called PAK_P3, scientists measured bacterial and viral RNA transcripts and metabolites during the course of a viral infection. They showed that the phage causes bacterial RNAs to rapidly degrade, then scavenges the available pyrimidine nucleotides for its own use. The PAK_P3 phage also uses RNA-based strategies to regulate its gene expression, using antisense transcripts and small noncoding RNA. Overall, the findings highlight the prominent role of RNA metabolism in the bacteriophage's infection strategy.

The new study combines "omics" techniques with traditional microbiology to give a detailed picture of how a virus subverts its host cell, both metabolically and genetically, to replicate itself. PAK_P3 is representative of a new group of viruses with promising characteristics for future therapeutic use, and its host, P. aeruginosa, is commonly multi-drug resistant, making it a desirable target for phage therapy. Before bacteriophages can be used effectively in medicine, however, a better understanding of their lifecycles will be necessary to establish protocols for their safe and proper use.


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Citation: Chevallereau A, Blasdel BG, De Smet J, Monot M, Zimmermann M, Kogadeeva M, et al.(2016) Next-Generation "-omics" Approaches Reveal a Massive Alteration of Host RNA Metabolism during Bacteriophage Infection of Pseudomonas aeruginosa. PLoS Genet 12(7): e1006134. doi:10.1371/journal. pgen.1006134

Image and Video Credit: Anne Chevallereau and colleagues

Funding: This research was supported by the Geconcerteerde Onderzoeks Actie grant 'Phage Biosystems' from the KULeuven. BGB has a PhD scholarship within the framework of an Onderzoeks Toelage grant of the KULeuven. AC was supported by PhD fellowships from the Ministère de l'Enseignement Supérieur et de la Recherche; ED N° 516 B3MI Paris Diderot University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

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