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Review
. 2021 Apr:68:23-29.
doi: 10.1016/j.copbio.2020.09.009. Epub 2020 Oct 23.

Phage engineering and the evolutionary arms race

Affiliations
Review

Phage engineering and the evolutionary arms race

Huan Peng et al. Curr Opin Biotechnol. 2021 Apr.

Abstract

Phages are versatile agents for delivering a variety of cargo, including nanomaterials, nucleic acids, and small molecules. A potentially important application is treatment of antibiotic-resistant infections. All of these applications require molecular engineering of the phages, including chemical modification and genetic engineering. Phages are remarkably amenable to such engineering. We review some examples, including for controlled phage therapy. We suggest that the ability of phages to support extensive engineering may have evolutionary origins in the billions-year-old 'arms race' between bacteria and phages, which selects for sequences and structures that are robust in the face of rapid evolutionary change. This leads to high tolerance of both naturally evolved mutations and synthetic molecular engineering.

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Conflict of interest statement

Conflict of interest statement

Nothing declared.

Figures

Figure 1.
Figure 1.
The evolutionary arms race between bacteria and phage drives a rapid evolutionary pace (A). The resulting phage scaffolds were presumably selected for tolerance to mutations. A correlated trait is tolerance to other chemical modifications, such as those used in molecular engineering (B).

References

    1. Westwater C, Kasman LM, Schofield DA, Werner PA, Dolan JW, Schmidt MG, and Norris JS (2003). Use of Genetically Engineered Phage To Deliver Antimicrobial Agents to Bacteria: an Alternative Therapy for Treatment of Bacterial Infections. Antimicrobial Agents and Chemotherapy 47, 1301–1307. - PMC - PubMed
    1. Dąbrowska K (2019). Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review. Medicinal Research Reviews 39, 2000–2025. - PMC - PubMed
    1. Haaber J, Leisner JJ, Cohn MT, Catalan-Moreno A, Nielsen JB, Westh H, Penades JR, and Ingmer H (2016). Bacterial viruses enable their host to acquire antibiotic resistance genes from neighbouring cells. Nature communications 7, 13333. - PMC - PubMed
    1. Waldor MK, and Mekalanos JJ (1996). Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272, 1910–1914. - PubMed
    1. Tarafder AK, von Kugelgen A, Mellul AJ, Schulze U, Aarts D, and Bharat TAM (2020). Phage liquid crystalline droplets form occlusive sheaths that encapsulate and protect infectious rod-shaped bacteria. Proc Natl Acad Sci U S A 117, 4724–4731.

      • • Filamentous phages are associated with the biofilms of the prominent lung and wound pathogen P. aeruginosa. This work shows that the virions increase antibiotic resistance by physically encasing P. aeruginosa cells in a protective sheath. This illustrates how some phages enhance bacterial fitness, a concern for phage therapy that must be addressed through molecular engineering.

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