Phages trigger antiviral responses, helping bacteria to evade the immune system

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Pseudomonas aeruginosa uses a phage to trick the host’s immune system into ignoring it, in turn suppressing bacterial clearance from infected wounds, according to new research.

The phage, called Pf, prompts an inappropriate antiviral response form the host, in turn allowing bacterial infection. This directly pathogenic role for phage virions has been previously unsuspected.

In the study, published recently in Science, the symbiotic relationship of P. aeruginosa and Pf was investigated. Pf is a temperate phage, which co-exist inside bacteria without killing them and this trait has previously led scientists to suspect the phages are advantageous to the bacteria in some way.

In this investigation the team, led by Paul Bollyky (Stanford University, CA, USA), collected swabs from chronic wounds in 111 individuals, of these 37 had a P. aeruginosa infection. Assessing the P. aeruginosa infections, 68% were discovered to contain the Pf virus and those with Pf wew commonly more chronic, non-helaing wounds.

To assess this further the phage-infected bacteria from the wounds were transferred into open wounds on mouse models. The researchers observed that it took 50-times fewer bacteria to establish an infection, and that survival rate was poorer when phage-infected P. aeruginosa was used, compared with P. aeruginosa alone.

Delving into the mechanism behind this finding, the team discovered that PF-infected P. aeruginosa attracted phagocytes to the wound, however, once phagocytes had ingested infected bacteria triggered an antiviral response, rather than an antibacterial. The researchers suggest this could be due to the phages producing RNA on uptake to phagocytes, which triggered TLR3 and TRIF-dependent type I interferon expression.

Consistent with a pathogenic role for Pf, the team demonstrated that by vaccinating the mice against Pf before infecting them with PF-infected P. aeruginosa infections were reduced. Transfer of antiphage antibodies also appeared to be protective.

This paper is the first to suggest phages could harm human health, although it should be noted that phages often used therapeutically against antibiotic-resistant infections are lytic phages, and thus more research will be required to understand if these mechanisms are also present in this subtype.

As a next step, Bollyky and his group are working on the translational aspects of their finding; they have patented the Pf vaccine and are testing it in pigs that have burns or skin wounds.

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Source: Sweere JM, Van Belleghem JD, Ishak H et al. Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection. Science 363, 6434 (2019).

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