Reprogramming bacteriophage host range: design principles and strategies for engineering receptor binding proteins

Matthew Dunne, Nikolai S. Prokhorov, Martin J. Loessner, Petr G. Leiman

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

Bacteriophages (phages) use specialized tail machinery to deliver proteins and genetic material into a bacterial cell during infection. Attached at the distal ends of their tails are receptor binding proteins (RBPs) that recognize specific molecules exposed on host bacteria surfaces. Since the therapeutic capacity of naturally occurring phages is often limited by narrow host ranges, there is significant interest in expanding their host range via directed evolution or structure-guided engineering of their RBPs. Here, we describe the design principles of different RBP engineering platforms and draw attention to the mechanisms linking RBP binding and the correct spatial and temporal attachment of the phage to the bacterial surface. A deeper understanding of these mechanisms will directly benefit future engineering of more effective phage-based therapeutics.

Original languageEnglish (US)
Pages (from-to)272-281
Number of pages10
JournalCurrent Opinion in Biotechnology
Volume68
DOIs
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

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