Targeting mechanisms of tailed bacteriophages


Phages differ substantially in the bacterial hosts that they infect. Their host range is determined by the specific structures that they use to target bacterial cells. Tailed phages use a broad range of receptor-binding proteins, such as tail fibres, tail spikes and the central tail spike, to target their cognate bacterial cell surface receptors. Recent technical advances and new structure–function insights have begun to unravel the molecular mechanisms and temporal dynamics that govern these interactions. Here, we review the current understanding of the targeting machinery and mechanisms of tailed phages. These new insights and approaches pave the way for the application of phages in medicine and biotechnology and enable deeper understanding of their ecology and evolution.

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Fig. 1: Representative structures of tailed phages.
Fig. 2: Model of phage T4 adsorption to the host surface.

Adapted with permission from ref.4, Proceedings of the National Academy of Sciences of the United States of America.

Fig. 3: Receptor-binding proteins of tailed phages.
Fig. 4: Gram-negative and Gram-positive bacterial receptors for the attachment of tailed phages.


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F.L.N. is supported by the Netherlands Organization for Scientific Research (NWO) Veni grant 016.Veni.181.092. P.A.d.J. and B.E.D. are supported by NWO Vidi grant 864.14.004. H.J.E.B. and L.L.D. are supported by the NWO/OCW as part of the Frontiers of Nanoscience programme. R.L. is supported by a Concerted Research Actions (GOA) grant from KU Leuven. S.J.J.B. is supported by NWO Vidi grant 864.11.005, European Research Council (ERC) Stg grant 639707 and a TU Delft start-up grant.

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F.L.N., L.L.D. and S.J.J.B. researched the data for the article. H.J.E.B., R.L., B.E.D. and S.J.J.B. provided substantial contribution to discussions of the content. F.L.N., M.V., P.A.J. and L.L.D. wrote the article. F.L.N., H.J.E.B., R.L., B.E.D. and S.J.J.B. reviewed and edited the manuscript before submission.

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Phages, or bacteriophages, are viruses that specifically infect bacteria for survival and replication.


Proteins that assemble together to form a complex that acts as a channel (pore) across membranes through which molecules can diffuse.


A protein structure found in tailed phages from the Myoviridae and Siphoviridae families. Tails and tail appendages, including tail fibres or tail spikes, attach to the baseplate.


Stable (relatively) forms of phage in which the genome is integrated into, and replicated with, the genome of the bacterial host, without lysis of the bacterial cell; prophages may also exist as extrachromosomal plasmids.


Repetitive glycan polymers that constitute the outermost domain of the lipopolysaccharide of Gram-negative bacteria.

Genetic plasticity

The alterable nature of genomes that enables the exchange of nucleic acids from one organism to another, usually to adapt to new environmental conditions.


A protein structure formed by parallel polypeptide chains associated in a helical pattern with either two or three faces; may be left-handed or right-handed.

Vi capsule

A bacterial capsule that exposes the Vi antigen, a heat-labile somatic antigen thought to be associated with virulence in some bacteria.


The removal of an acetyl group from a chemical compound.


The process by which genetic material is exchanged between DNA molecules.


A protein composed of three identical units of polypeptide.


An individual molecule that can associate with similar molecules to form a larger molecule (dimer, trimer and polymer).


Proteins that interact with and assist in the folding and unfolding or assembly and disassembly of other proteins without being part of the final structure.


A right-handed coiled conformation of proteins in which the resulting structure resembles a helix.


The breakdown (hydrolysis) of proteins or peptides into their key components, peptides and amino acids, by the action of enzymes.

Phage tail-like complexes

Protein complexes that are homologous to phage tails and facilitate the killing of cells or influence bacterial and eukaryotic cells through physical interactions.


The orientation, by growth or movement, of all or part of an organism to an external stimulus.

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Nobrega, F.L., Vlot, M., de Jonge, P.A. et al. Targeting mechanisms of tailed bacteriophages. Nat Rev Microbiol 16, 760–773 (2018).

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