Bacteriophages (phages) are often described as obligate predators of their bacterial hosts, and phage predation is one of the leading forces controlling the density and distribution of bacterial populations. Every 48 h half of all bacteria on Earth are killed by phages. Efficient killing also forms the basis of phage therapy in humans and animals and the use of phages as food preservatives. In turn, bacteria have a plethora of resistance systems against phage attack, but very few bacterial species, if any, have entirely escaped phage predation. However, in complex communities and environments such as the human gut, this antagonistic model of attack and counter-defence does not fully describe the scope of phage–bacterium interactions. In this Review, we explore some of the more mutualistic aspects of phage–bacterium interactions in the human gut, and we suggest that the relationship between phages and their bacterial hosts in the gut is best characterized not as a fight to the death between enemies but rather as a mutualistic relationship between partners.
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A.N.S. was supported by a Wellcome Trust Research Career Development Fellowship (220646/Z/20/Z) and the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 101001684). C.J.T. and C.H. were supported by Science Foundation Ireland under grant no. SFI/12/RC/2273.
The authors declare no competing interests.
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- Abortive infection systems
Bacterial toxin–antitoxin systems that prevent the completion of the viral infection through facilitating suicide of the infected bacterial cell.
- Lysogenic conversion
Alteration in bacterial phenotypes following temperate bacteriophage infection via expression of genes encoded within the bacteriophage genome.
- Horizontal gene transfer
(HGT). The transfer of genes between organisms that does not involve their direct passing to progeny through replication.
Vessels used for the continuous culture of microorganisms via constant maintenance of conditions required for growth (for example, nutrient levels).
- Gnotobiotic animals
Animals free of microbial colonization.
- Phase variation
Genetic phenomenon characterized by the stochastic, high-frequency, reversible alteration in gene expression.
- Arms race dynamics
The continuous and reciprocal co-evolutionary adaptions that occur between bacteriophages and their bacterial hosts. Bacteria develop means to prevent infection (such as removal or alteration of receptors), whereas bacteriophages adapt to overcome bacterial defences (such as targeting different bacterial receptors).
- Fluctuating selection
Transient oscillations in genotype frequencies within phage and bacterial communities via negative frequency-dependent selection. Here, bacteriophages evolve to infect common bacterial genotypes, resulting in a selective advantage for low-frequency bacterial resistance alleles and therefore enabling those rare alleles to increase in frequency. As bacterial subpopulations with an allele rise in abundance, they become the focus of bacteriophage infectivity evolution, driving diversification of bacteriophage infectivity, and again providing a selective advantage for rare bacterial genotypes, causing the cycle to continue.
- Diversity-generating retroelements
Genetic elements able to accelerate mutation rates within specific genomic regions through error-prone reverse transcription.
- Piggyback-the-winner model
A model that describes a cooperative relationship between bacteria and temperate bacteriophages, via lysogeny, that is believed to dominate when bacterial densities are high. Temperate bacteriophages ‘piggyback’ on the success of a high-density bacterial host through lysogenic infection so that the bacteriophage replicates together with the host genome and is maintained in the population. At the same time, lysogenic infection of this already ‘winning’ bacterial host can enable the bacterium to receive further competitive advantages via lysogenic conversion and superinfection exclusion.
- Superinfection immunity
Bacterial resistance to secondary bacteriophage infection that results from an existing bacteriophage infection.
- Peyer patches
Lymphoid follicles in the small intestine involved in organizing immune responses to luminal antigens.
- Gene transfer agents
Gene delivery systems that can package random sections of host DNA and transfer them to another cell.
- Black Queen hypothesis
A hypothesis proposing that reductive genome evolution is acceptable through a ‘leaky’ common good function, wherein reductions in each organism’s genome can be offset by the presence of corresponding regions within the genomes of other members of a wider population.
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Shkoporov, A.N., Turkington, C.J. & Hill, C. Mutualistic interplay between bacteriophages and bacteria in the human gut. Nat Rev Microbiol 20, 737–749 (2022). https://doi.org/10.1038/s41579-022-00755-4
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