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Cited by 19Bacteriophages and microbial interactionsBacterial Genetics and BiotechnologyEvolution and Genetic Dynamics

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Multicopy suppressor screens reveal convergent evolution of single-gene lysis proteins

Open access
Adler, Benjamin A., Chamakura, Karthik, Carion, Heloise, Krog, Jonathan, Deutschbauer, Adam M., Young, Ry, Mutalik, Vivek K., Arkin, Adam P.·2023·Nature Chemical Biology
DOI 10.1038/s41589-023-01269-7PMC PMC10229422
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Abstract

Single-strand RNA (ssRNA) Fiersviridae phages cause host lysis with a product of single gene (sgl for single-gene lysis; product Sgl) that induces autolysis. Many different Sgls have been discovered, but the molecular targets of only a few have been identified. In this study, we used a high-throughput genetic screen to uncover genome-wide host suppressors of diverse Sgls. In addition to validating known molecular mechanisms, we discovered that the Sgl of PP7, an ssRNA phage of Pseudomonas aeruginosa, targets MurJ, the flippase responsible for lipid II export, previously shown to be the target of the Sgl of coliphage M. These two Sgls, which are unrelated and predicted to have opposite membrane topology, thus represent a case of convergent evolution. We extended the genetic screens to other uncharacterized Sgls and uncovered a common set of multicopy suppressors, suggesting that these Sgls act by the same or similar mechanism.

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  • Recent technologies for bacterial phenotyping and phage receptor identification enable predictive modeling.

    “Recent technologies for bacterial phenotyping and phage receptor identification enable predictive modeling [90,151–156]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [151]

    The Main section describes Dub-seq as a scalable method for bacterial fitness assays, supporting the bacterial-phenotyping portion. The Results section names receptors used by several phages, but does not describe a technology for identifying phage receptors; neither passage says these technologies enable predictive modeling. Page numbers are unavailable in our copy. (LLM, conf=0.82)

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Research works printed but not linked: 39

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Metadata

Authors
Adler, B. A., Chamakura, K., Carion, H., Krog, J., Deutschbauer, A. M., Young, R., Mutalik, V. K., & Arkin, A. P.
Affiliations
  • University of California, San Francisco (US)
  • Armata Pharmaceuticals (United States) (US)
  • University of California, Berkeley (US)
  • Lawrence Berkeley National Laboratory (US)
  • Texas A&M University (US)
Corresponding author
  • Mutalik, Vivek K.
  • Arkin, Adam P.
ORCID
Venue
Nature Chemical Biology
Publisher
Springer Science and Business Media LLC
Published
2023-02-20
Volume
19
Issue
6
Pages
759-766
ISSN
  • 1552-4450 (ISSN-L)
  • 1552-4469
DOI
10.1038/s41589-023-01269-7
PMC
PMC10229422
OpenAlex
W4321369597
Cited by
19
References
1
Citations by year
2026: 4 · 2025: 2 · 2024: 7 · 2023: 5
FWCI
2.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Chemical Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • Microbiology Program of the Innovative Genomics Institute, Berkeley
  • U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R35GM136396)
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
convergent evolution, multicopy suppressor screen, Pseudomonas aeruginosa, MurJ, flippase, phage-host interactions, membrane topology
MeSH terms
Bacteriophages, Biological Evolution, Genes, Viral, Pseudomonas aeruginosa

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