A novel T4- and λ-based receptor binding protein family for bacteriophage therapy host range engineering.


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Authors
Magaziner, Samuel J 
Salmond, George PC 
Abstract

Widespread multidrug antimicrobial resistance in emerging pathogens has led to a renewed interest in phage therapy as an alternative or supplement to traditional small molecule drugs. The primary limiting factors of phage therapy deployment rest in the narrow host range specificity of phage as well as a poor understanding of many phages' unintended downstream effects on host physiology and microbiota as well as on adverse pathogen evolution. Consequently, this has made assembling well-defined and safe "phage-cocktails" of solely naturally occurring phages labor- and time-intensive. To increase the speed, efficacy, and safety of therapeutic deployment, there is exceptional interest in modulating the host ranges of well-characterized lytic phages (e.g., T4 and T7) by using synthetic strategies to the swap phage tail components, the receptor binding proteins (RBPs) key for host specificity. Here we identify the RBP of the Citrobacter rodentium temperate phage ΦNP as ORF6. Through bioinformatic and phylogenetic assays, we demonstrate this RBP to be closely related to the known RBPs of T4 and λ. Further investigation reveals a novel, greater than 200 members RBP family with phages targeting several notable human pathogens, including Klebsiella pneumoniae, Escherichia coli O157:H7, Salmonella spp., and Shigella spp. With well characterized lytic members, this RBP family represents an ideal candidate for use in synthetic strategies for expanding therapeutic phage host ranges.

Description

Peer reviewed: True


Acknowledgements: We would like to acknowledge the other members of the Salmond Laboratory, especially Rita Monson and lab alumni Ray Chai and Bihe Chen for their kind and helpful discussion.

Keywords
Microbiology, bacteriophage, receptor binding proteins, antimicrobial resistance, phage therapy and biotechnology, phage T4, phage λ, Citrobacter rodentium
Journal Title
Front Microbiol
Conference Name
Journal ISSN
1664-302X
1664-302X
Volume Title
Publisher
Frontiers Media SA