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Cited by 52Bacteriophages and microbial interactionsBacterial Genetics and BiotechnologyEvolution and Genetic Dynamics

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Small protein modules dictate prophage fates during polylysogeny

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Silpe, Justin E., Duddy, Olivia P., Johnson, Grace E., Beggs, Grace A., Hussain, Fatima A., Forsberg, Kevin J., Bassler, Bonnie L.·2023·Nature
DOI 10.1038/s41586-023-06376-yPMC PMC10432266

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Abstract

Most bacteria in the biosphere are predicted to be polylysogens harbouring multiple prophages 1–5 . In studied systems, prophage induction from lysogeny to lysis is near-universally driven by DNA-damaging agents 6 . Thus, how co-residing prophages compete for cell resources if they respond to an identical trigger is unknown. Here we discover regulatory modules that control prophage induction independently of the DNA-damage cue. The modules bear little resemblance at the sequence level but share a regulatory logic by having a transcription factor that activates the expression of a neighbouring gene that encodes a small protein. The small protein inactivates the master repressor of lysis, which leads to induction. Polylysogens that harbour two prophages exposed to DNA damage release mixed populations of phages. Single-cell analyses reveal that this blend is a consequence of discrete subsets of cells producing one, the other or both phages. By contrast, induction through the DNA-damage-independent module results in cells producing only the phage sensitive to that specific cue. Thus, in the polylysogens tested, the stimulus used to induce lysis determines phage productivity. Considering the lack of potent DNA-damaging agents in natural habitats, additional phage-encoded sensory pathways to lysis likely have fundamental roles in phage–host biology and inter-prophage competition.

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Metadata

Authors
Silpe, J. E., Duddy, O. P., Johnson, G. E., Beggs, G. A., Hussain, F. A., Forsberg, K. J., & Bassler, B. L.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Princeton University (US)
  • Massachusetts Institute of Technology (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Bassler, Bonnie L.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2023-07-26
Volume
620
Issue
7974
Pages
625-633
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-023-06376-y
PMC
PMC10432266
OpenAlex
W4385286173
Cited by
52
References
2
Citations by year
2026: 19 · 2025: 15 · 2024: 11 · 2023: 5
FWCI
8.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (1713731)
  • Damon Runyon Cancer Research Foundation (DRG-2468-22)
  • Princeton University
  • Broad Institute
  • Universität Wien
  • National Institutes of Health (1DP2-AI154402)
  • National Institute of General Medical Sciences (T32GM007388, F32GM149034, R37GM065859)
  • National Institute of Allergy and Infectious Diseases (DP2AI154402)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Keywords
prophage induction, transcription factors, DNA damage, phage-host interactions
MeSH terms
Bacteria, Bacteriophages, DNA Damage, DNA, Viral, Lysogeny, Transcription Factors, Viral Proteins, Virus Activation, Prophages, Host-Pathogen Interactions, Single-Cell Analysis

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