Diverse phage communities are maintained stably on a clonal bacterial host

Creators: Pyenson, Nora C.^{1, 2}; Leeks, Asher²; Nweke, Odera²; Goldford, Joshua E.³; Schluter, Jonas^{1, 4}; Turner, Paul E.²; Foster, Kevin R.⁵; Sanchez, Alvaro⁶

1. New York University
2. Yale University
3. California Institute of Technology
4. Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA.
5. University of Oxford
6. University of Salamanca

Abstract

Bacteriophages are the most abundant and phylogenetically diverse biological entities on Earth, yet the ecological mechanisms that sustain this extraordinary diversity remain unclear. In this study, we discovered that phage diversity consistently outstripped the diversity of their bacterial hosts under simple experimental conditions. We assembled and passaged dozens of diverse phage communities on a single, nonevolving strain of Escherichia coli until the phage communities reached equilibrium. In all cases, we found that two or more phage species coexisted stably, despite competition for a single, clonal host population. Phage coexistence was supported through host phenotypic heterogeneity, whereby bacterial cells adopting different growth phenotypes served as niches for different phage species. Our experiments reveal that a rich community ecology of bacteriophages can emerge on a single bacterial host.

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Acknowledgement

We would like to thank members of the Schluter, Sanchez, Turner, and Foster Labs for their helpful discussion. This research made use of the Science Hill Flow Cytometry Facility at Yale University.

Funding

This research was supported by the Packard Foundation Fellowship (A.S. and N.C.P.), the Simons Foundation through the Life Science Research Foundation Postdoctoral Fellowship (N.C.P.), European Research Council grant 787932 (K.R.F.), Wellcome Trust Investigator Award 209397/Z/17/Z (K.R.F.), the James S. McDonnell Foundation Postdoctoral Fellowship (A.L.), National Aeronautics and Space Administration (NASA) Interdisciplinary Consortia for Astrobiology Research grant 80NSSC23K1357 (J.E.G.), and NIH grant DP2 AI164318-01 (J.S.). A.S. acknowledges support from grant PID2021-125478NAI00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF: A way of making Europe,” as well as funding by the European Union (ERC, ECOPROSPECTOR, 101088469).

Contributions

Conceptualization: N.C.P., K.R.F., and A.S. Methodology: N.C.P., J.E.G., A.L., and A.S. Formal analysis: N.C.P. and A.L. Investigation: N.C.P. and O.N. Writing – original draft: N.C.P. and A.L. Writing – review and editing: N.C.P., A.L., P.E.T., K.R.F., and A.S.

Conflict of Interest

J.S. is cofounder of Postbiotics Plus Research and serves on an advisory board of and holds equity in Jona Health. J.S. is an inventor on patent application no. 63/299,607 held by Postbiotics Plus Research that covers microbiome therapeutics.

Data Availability

Genome sequences for species in our phage collection are deposited at NCBI GenBank under accession numbers PP925821-PP925847 (see also table S1). The contigs generated from sequencing of phage communities and the code used to analyze the community composition are deposited at Dryad (43) as are the alternate phylogenetic trees generated by the VICTOR tree builder.

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