This journal article review looks at a study published on the topic of bacteriophage and their mechanism of host specificity:

Journal Citation:

Plattner M, Shneider MM, Arbatsky NP, Shashkov AS, Chizhov AO, Nazarov S, Prokhorov NS, Taylor NM15, Buth SA, Gambino M, Gencay YE, Brøndsted L, Kutter EM, Knirel YA, Leiman PG. Structure and Function of the Branched Receptor-Binding Complex of Bacteriophage CBA120. J Mol Biol. 2019 Jul 17. pii: s0022-2836(19)30452-8. doi: 10.1016/j.jmb.2019.07.022. PMID: 31325442


Bacteriophages recognize their host cells with the help of tail fiber and tailspike proteins that bind, cleave, or modify certain structures on the cell surface. The spectrum of ligands to which the tail fibers and tailspikes can bind is the primary determinant of the host range. Bacteriophages with multiple tailspike/tail fibers are thought to have a wider host range than their less endowed relatives but the function of these proteins remains poorly understood. Here, we describe the structure, function, and substrate specificity of three tailspike proteins of CBA120 – TSP2, TSP3, and TSP4 (orf211 through orf213, respectively). We show that tailspikes TSP2, TSP3, and TSP4 are hydrolases that digest the O157, O77, and O78 Escherichia coli O-antigens, respectively. We demonstrate that recognition of the Escherichia coli O157:H7 host by CBA120 involves binding to and digesting the O157 O-antigen by TSP2. We report the crystal structure of TSP2 in complex with a repeating unit of the O157 O-antigen. We demonstrate that according to the specificity of its tailspikes TSP2, TSP3, and TSP4, CBA120 can infect E. coli O157, O77, O78, respectively. We also show that CBA120 infects Salmonella enterica serovar Minnesota and this host range expansion is likely due to the function of TSP1. Finally, we describe the assembly pathway and the architecture of the TSP1-TSP2-TSP3-TSP4 branched complex in CBA120 and its related ViI-like phages.

Reviewer’s comments:

This is a valuable article for both the student and the expert. The introduction provides a review of some basic phage anatomy, and focuses our attention on how this anatomy is related to the larger question of how bacteriophage came to be so specific in their host selection. Why do some species attack a wide variety of bacteria, while others attack only one subtype of one species of bacteria? How does the phage “select” its host? To answer these questions, just keep reading. Using a variety of molecular and biochemical (protein chemistry) techniques, the researchers demonstrated that the molecular composition and sequence of the various tail spike proteins (TSPs) of phage CBA120 confer not simply host binding specificity but also the hydrolysis that ultimately breaks down very specific protein components of the host’s cell membrane. For example, CBA120 phage infects Escherichia coli O157:H7 because the phage’s TSP2 binds and digests (hydrolyzes) the O157 protein. Similarly, TSP3 binds and digests E. coli O77 protein, and TSP4 binds and digests E. coli O78 protein. Knowing the specific surface proteins that the TSPs will bind and hydrolyze may someday provide easier methods to predict – or even engineer – phage host specificity.