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bioRxiv · 10.1101/2023.10.03.560654

Engineering of Salmonella phages into novel antimicrobial Tailocins

Woudstra, C.·Sorensen, A. N.·Brondsted, L.
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Abstract

Due to the extensive use of antibiotics, the increase of infections caused by antibiotic resistant bacteria are now a global health concern. Phages have proven useful for treating bacterial infections and represent a promising alternative or complement to antibiotic treatment. Yet, other alternative exists, such as bacteria-produced non-replicative protein complexes that can kill their targeted bacteria by puncturing their membrane (Tailocins). To expand the repertoire of Tailocins available, we suggest a new approach transforming phages into Tailocins. Here we genetically engineered the virulent Ackermannviridae phage S117, as well as temperate phages Fels-1, -2 and Gifsy-1 and -2 targeting the food pathogen Salmonella, by deleting the portal vertex or major capsid gene using CRISPR-Cas9. We report the production of Tailocin particles from engineered virulent and temperate phages able to kill their native host. Our work represents a steppingstone to tape into the huge diversity of phages and transform them into versatile puncturing new antimicrobials.

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Woudstra, C., Sorensen, A. N., Brondsted, L.. 2023-10-03. Engineering of Salmonella phages into novel antimicrobial Tailocins. https://doi.org/10.1101/2023.10.03.560654

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