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  • Review Article
  • Published:

Bacteriophage resistance mechanisms

Nature Reviews Microbiology volume 8, pages 317–327 (2010)Cite this article

Subjects

Key Points

  • Phages (bacterial viruses) are the most numerous microorganisms on Earth. Bacteria have developed an astonishing array of strategies to combat these viruses at each step of the infection process. Here we describe these strategies and how phages have adapted to subvert them.

  • Phage adsorption to cell receptors is the initial step of infection, and some bacterial strains have developed mechanisms to prevent this key process. There are at least three strategies used by adsorption-blocking systems: receptor blocking, extracellular matrix production and competitive inhibitor production.

  • Superinfection exclusion (Sie) systems prevent phage DNA entry into the host cell, thereby conferring bacterial immunity against superinfecting phages. Several mechanisms that inhibit phage DNA injection have been uncovered in Gram-negative and Gram-positive bacteria.

  • The notorious bacterial restriction–modification systems prevent phage infection by cleaving phage genomic DNA. As a response, phages have evolved by specifically modifying their genomes to avoid DNA cleavage. This ongoing battle of co-evolution between bacteria and phages is exemplified by the canonical coliphage T4.

  • Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (cas) genes are new fascinating topics. The bacterial and archeal CRISPR–Cas systems confer immunity against incoming foreign DNA such as phage genomes. A likely mode of action of this mechanism has been proposed, along with phage strategies to circumvent this system.

  • Bacteria have also evolved a plethora of intracellular proteins that cause abortion of the phage infection. These antiphage mechanisms target crucial steps of phage multiplication, such as transcription, protein synthesis, maturation and host cell lysis. Several different abortive infection (Abi) systems have been found, and the mode of action has been studied for a few of these.

Abstract

Phages are now acknowledged as the most abundant microorganisms on the planet and are also possibly the most diversified. This diversity is mostly driven by their dynamic adaptation when facing selective pressure such as phage resistance mechanisms, which are widespread in bacterial hosts. When infecting bacterial cells, phages face a range of antiviral mechanisms, and they have evolved multiple tactics to avoid, circumvent or subvert these mechanisms in order to thrive in most environments. In this Review, we highlight the most important antiviral mechanisms of bacteria as well as the counter-attacks used by phages to evade these systems.

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Figure 1: The phage replication cycle.
Figure 2: Different strategies used by bacteria to block phage adsorption.
Figure 3: Blocking phage DNA entry into the bacterial cell.
Figure 4: The arms race between bacteria and phages.
Figure 5: The CRISPR (clustered regularly interspaced short palindromic repeat) mode of action.
Figure 6: The mode of action of the Rex system.

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Acknowledgements

We thank B.-A. Conway for editorial assistance. S.J.L. was a recipient of a graduate scholarship from the Natural Sciences and Engineering Research Council (NSERC) of Canada. J.E.S. is a recipient of a graduate scholarship from the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT). S.M. would like to acknowledge the funding support of NSERC, FQRNT, the Canadian Institutes of Health Research, Novalait, Agropur and Danisco.

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Authors and Affiliations

  1. Department of Civil & Environmental Engineering, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Simon J. Labrie

  2. Département de biochimie et de microbiologie, Faculté des sciences et de génie, Université Laval,

    Julie E. Samson & Sylvain Moineau

  3. Groupe de recherche en écologie buccale, Faculté de médecine dentaire, Université Laval,

    Julie E. Samson & Sylvain Moineau

  4. Félix d'Hérelle Reference Center for Bacterial Viruses, Université Laval, Québec City, G1V 0A6, Québec, Canada

    Julie E. Samson & Sylvain Moineau

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Correspondence to Sylvain Moineau.

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Glossary

Phase variation

A genetically programmed biological phenomenon that occurs in bacteria that need to adapt to different environments. These bacteria can modify their cellular components according to environmental conditions through the regulation of a complex gene expression network.

Receptor-binding complex

A phage-encoded structural protein complex that is essential for the adsorption of the phage to the bacterial cell. In tailed phages, this complex is located at the extremity of the tail.

O antigen

The outer-most part of the lipopolysaccharide on the bacterial outer membrane, containing a repetitive glycan polymer. A great diversity is observed in the structure of E. coli O antigens, and they are good targets for serotyping methods and phages.

K antigen

Polysaccharide in the bacterial capsule.

Restriction enzyme

An endonuclease protects the bacterial cell against infection by cleaving foreign DNA at specific sites. These enzymes are generally coupled with a cognate DNA methylase, which modifies and protects the host DNA.

Two-component system

A biological mechanism necessitating the presence of two enzymes to be functional.

Cryptic genetic element

An incomplete or defective prophage that is unable to excise from the host genome and multiply as a result of host genome evolution. Such prophages provide a pool of phage genes that can be tapped into by an incoming virulent phage.

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Labrie, S., Samson, J. & Moineau, S. Bacteriophage resistance mechanisms. Nat Rev Microbiol 8, 317–327 (2010). https://doi.org/10.1038/nrmicro2315

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