Preprint Review Version 1 This version is not peer-reviewed

The Ecology of Phage Resistance: The Key to Successful Phage Therapy?

Version 1 : Received: 13 May 2020 / Approved: 14 May 2020 / Online: 14 May 2020 (08:09:04 CEST)

How to cite: Gittrich, M.; Liu, Y.; Tian, F.; Crouch, A.; Jang, H.B.; Du, J.; Sullivan, M. The Ecology of Phage Resistance: The Key to Successful Phage Therapy?. Preprints 2020, 2020050232 (doi: 10.20944/preprints202005.0232.v1). Gittrich, M.; Liu, Y.; Tian, F.; Crouch, A.; Jang, H.B.; Du, J.; Sullivan, M. The Ecology of Phage Resistance: The Key to Successful Phage Therapy?. Preprints 2020, 2020050232 (doi: 10.20944/preprints202005.0232.v1).

Abstract

: As antibiotic resistance undermines efforts to treat bacterial infections, phage therapy is being increasingly considered as an alternative in clinical settings and agriculture. However, a major concern in using phages is that pathogens will develop resistance to the phage. Due to the constant evolutionary pressure by phages, bacteria have evolved numerous mechanisms to block infection. If we determine the most common among them, we could use this knowledge to guide phage therapeutics. Here we compile data from 88 peer-reviewed studies where phage resistance was experimentally observed and linked to a bacterial gene, then assessed these data for patterns. In total, 141 host genes were identified to block infection against one or more of 80 phages (representing five families of the Caudovirales) across 16 microbial host genera. These data suggest that bacterial phage resistance is diverse, but even well-studied systems are understudied, and there are gaping holes in our knowledge of phage resistance across lesser-studied regions of microbial and viral sequence space. Fortunately, scalable approaches are newly available that, if broadly adopted, can provide data to power ecosystem-aware models that will guide harvesting natural variation towards designing effective, broadly applicable phage therapy cocktails as an alternative to antibiotics.

Subject Areas

phage resistance; phage therapy; vConTACT 2.0; phage resistance ecology; bacteriophages

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