Genetic manipulation of Patescibacteria provides mechanistic insights into microbial dark matter and the epibiotic lifestyle
Open accessPublished version of a preprint
Abstract
Patescibacteria, also known as the candidate phyla radiation (CPR), are a diverse group of bacteria that constitute a disproportionately large fraction of microbial dark matter. Its few cultivated members, belonging mostly to Saccharibacteria, grow as epibionts on host Actinobacteria. Due to a lack of suitable tools, the genetic basis of this lifestyle and other unique features of Patescibacteira remain unexplored. Here, we show that Saccharibacteria exhibit natural competence, and we exploit this property for their genetic manipulation. Imaging of fluorescent protein-labeled Saccharibacteria provides high spatiotemporal resolution of phenomena accompanying epibiotic growth, and a transposon-insertion sequencing (Tn-seq) genome-wide screen reveals the contribution of enigmatic Saccharibacterial genes to growth on their hosts. Finally, we leverage metagenomic data to provide cutting-edge protein structure-based bioinformatic resources that support the strain Southlakia epibionticum and its corresponding host, Actinomyces israelii, as a model system for unlocking the molecular underpinnings of the epibiotic lifestyle.
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- Authors
- Wang, Y., Gallagher, L. A., Andrade, P. A., Liu, A., Humphreys, I. R., Turkarslan, S., Cutler, K. J., Arrieta-Ortiz, M. L., Li, Y., Radey, M. C., McLean, J. S., Cong, Q., Baker, D., Baliga, N. S., Peterson, S. B., & Mougous, J. D.
- Affiliations
- University of Washington (US)
- Institute for Systems Biology (US)
- Harold C. Simmons Comprehensive Cancer Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Mougous, Joseph D.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2023-10
- Volume
- 186
- Issue
- 22
- Pages
- 4803-4817.e13
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC10633639
- OpenAlex
- W4386498269
- Cited by
- 108
- References
- 11
- Citations by year
- 2026: 26 · 2025: 53 · 2024: 28 · 2023: 1
- FWCI
- 18.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (R01AI128215, R01AI141953, R01DE023810)
- NSF
- University of Washington
- U.S. Department of Defense
- Southwestern Medical Foundation
- HHMI
- Defense Threat Reduction Agency
- Bill and Melinda Gates Foundation (OPP1156262)
- National Science Foundation (IIBR-2042948, IOS-2050550, MCB-2105570)
- Welch Foundation (I-2095-20220331)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- Patescibacteria, Candidate Phyla Radiation, microbial dark matter, Saccharibacteria, natural competence, genetic engineering, epibiosis, Actinomyces israelii, transposon sequencing, fluorescent protein tagging
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