Using OMIC Techniques to Understand Phage Therapy Virus

July 6, 2016
Using OMIC Techniques to Understand Phage Therapy Virus
Bacteriophage life cycle [Anne Chevallereau and colleagues]

A research team led by scientists at the University of Leuven in Belgium and the Pasteur Institute in France has found that a bacteriophage infecting an opportunistic and clinically relevant bacterium metabolizes host RNA to replicate itself inside the cell. The findings were published recently in PLOS Genetics through an article entitled “Next-Generation -omics” Approaches Reveal a Massive Alteration of Host RNA Metabolism during Bacteriophage Infection of Pseudomonas aeruginosa.”

The researchers used metabolomic and transcriptomic analyses to look at a particular bacteriophage (PAK_P3), which infects P. aeruginosa and has been studied for its use in phage therapy—using naturally occurring viruses to treat bacterial infections—touted as a potential alternative to antibiotic treatment. Since little is known about phage lifecycles, outside of a few model species, the research team measured bacterial and viral RNA transcripts and metabolites during a viral infection. The investigators found that the phage causes bacterial RNAs to degrade rapidly, then scavenges the available pyrimidine nucleotides for its own use. Moreover, the PAK_P3 phage uses RNA-based strategies to regulate its gene expression, employing antisense transcripts and small noncoding RNA.

“We present here the first analysis coupling data obtained from global next-generation approaches, RNA-Sequencing, and metabolomics, to characterize interactions between the virulent bacteriophage PAK_P3 and its host Pseudomonas aeruginosa,” the authors wrote. “We detected a dramatic global depletion of bacterial transcripts coupled with their replacement by viral RNAs over the course of infection, eventually leading to drastic changes in pyrimidine metabolism.”

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.

“This process relies on host machinery hijacking as suggested by the strong up-regulation of one bacterial operon involved in RNA processing,” the authors penned. “Moreover, we found that RNA-based regulation plays a central role in PAK_P3 lifecycle as antisense transcripts are produced mainly during the early stage of infection and viral small non-coding RNAs are massively expressed at the end of infection.”

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 utilized effectively in medicine, however, a better understanding of their lifecycles will be necessary to establish protocols for their safe and proper use.

“This work highlights the prominent role of RNA metabolism in the infection strategy of a bacteriophage belonging to a new characterized sub-family of viruses with promising therapeutic potential,” the authors concluded.

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