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Pseudotyping Bacteriophage P2 Tail Fibers to Extend the Host Range for Biomedical Applications

Tabitha G. Cunliffe, Alan L. Parker, Alfonso Jaramillo

2022ACS Synthetic Biology16 citationsDOIOpen Access PDF

Abstract

phage P2 to alter its tropism toward pathogenic bacteria. Chimeric tail fibers formed between P2 and S16 genes were designed and generated through two approaches: homology- and literature-based. By presenting chimeric P2:S16 fibers on the P2 particle, our data suggests that the resultant phages were effectively detargeted from the native P2 cellular target, lipopolysaccharide, and were instead able to infect via the proteinaceous receptor, OmpC, the natural S16 receptor. Our work provides evidence that pseudotyping P2 is feasible and can be used to extend the host range of P2 to alternative receptors. Extension of this work could produce alternative chimeric tail fibers to target pathogenic bacterial threats. Our engineering of P2 allows adsorption through a heterologous outer-membrane protein without culturing in its native host, thus providing a potential means of engineering designer phages against pathogenic bacteria from knowledge of their surface proteome.

Topics & Concepts

BacteriophageMicrobiologyBiologyBacteriaEscherichia coliPathogenic bacteriaPeriplasmic spaceBacterial virusAntibiotic resistanceSynthetic biologyPhage therapyPilusAntibioticsGeneComputational biologyGeneticsBacteriophages and microbial interactionsMonoclonal and Polyclonal Antibodies ResearchRNA and protein synthesis mechanisms
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