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Title: Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes

Abstract

Bacteriophages from the Inoviridae family (inoviruses) are characterized by their unique morphology, genome content and infection cycle. One of the most striking features of inoviruses is their ability to establish a chronic infection whereby the viral genome resides within the cell in either an exclusively episomal state or integrated into the host chromosome and virions are continuously released without killing the host. To date, a relatively small number of inovirus isolates have been extensively studied, either for biotechnological applications, such as phage display, or because of their effect on the toxicity of known bacterial pathogens including Vibrio cholerae and Neisseria meningitidis. Here, we show that the current 56 members of the Inoviridae family represent a minute fraction of a highly diverse group of inoviruses. Using a machine learning approach leveraging a combination of marker gene and genome features, we identified 10,295 inovirus-like sequences from microbial genomes and metagenomes. Collectively, our results call for reclassification of the current Inoviridae family into a viral order including six distinct proposed families associated with nearly all bacterial phyla across virtually every ecosystem. Putative inoviruses were also detected in several archaeal genomes, suggesting that, collectively, members of this supergroup infect hosts across the domains Bacteriamore » and Archaea. Finally, we identified an expansive diversity of inovirus-encoded toxin–antitoxin and gene expression modulation systems, alongside evidence of both synergistic (CRISPR evasion) and antagonistic (superinfection exclusion) interactions with co-infecting viruses, which we experimentally validated in a Pseudomonas model. Capturing this previously obscured component of the global virosphere may spark new avenues for microbial manipulation approaches and innovative biotechnological applications.« less

Authors:
ORCiD logo [1]; ORCiD logo [2];  [3];  [4];  [1]; ORCiD logo [1];  [5]; ORCiD logo [5];  [1]; ORCiD logo [1];  [6];  [3]; ORCiD logo [1]; ORCiD logo [1];  [1]; ORCiD logo [1]
  1. USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)
  2. Inst. Pasteur, Paris (France)
  3. Colorado State Univ., Fort Collins, CO (United States)
  4. Univ. of California, San Francisco, CA (United States)
  5. Univ. of California, Berkeley, CA (United States)
  6. Univ. of California, San Francisco, CA (United States). Quantitative Biosciences Inst.
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Sciences Foundation (NSF); National Institutes of Health (NIH)
OSTI Identifier:
1581331
Grant/Contract Number:  
[AC02-05CH11231; EAR 1331940]
Resource Type:
Accepted Manuscript
Journal Name:
Nature Microbiology
Additional Journal Information:
[ Journal Volume: 4; Journal Issue: 11]; Journal ID: ISSN 2058-5276
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Archaea; Bacteriophages; Environmental microbiology; Phage biology; Metagenomics

Citation Formats

Roux, Simon, Krupovic, Mart, Daly, Rebecca A., Borges, Adair L., Nayfach, Stephen, Schulz, Frederik, Sharrar, Allison, Matheus Carnevali, Paula B., Cheng, Jan-Fang, Ivanova, Natalia N., Bondy-Denomy, Joseph, Wrighton, Kelly C., Woyke, Tanja, Visel, Axel, Kyrpides, Nikos C., and Eloe-Fadrosh, Emiley A. Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes. United States: N. p., 2019. Web. doi:10.1038/s41564-019-0510-x.
Roux, Simon, Krupovic, Mart, Daly, Rebecca A., Borges, Adair L., Nayfach, Stephen, Schulz, Frederik, Sharrar, Allison, Matheus Carnevali, Paula B., Cheng, Jan-Fang, Ivanova, Natalia N., Bondy-Denomy, Joseph, Wrighton, Kelly C., Woyke, Tanja, Visel, Axel, Kyrpides, Nikos C., & Eloe-Fadrosh, Emiley A. Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes. United States. doi:10.1038/s41564-019-0510-x.
Roux, Simon, Krupovic, Mart, Daly, Rebecca A., Borges, Adair L., Nayfach, Stephen, Schulz, Frederik, Sharrar, Allison, Matheus Carnevali, Paula B., Cheng, Jan-Fang, Ivanova, Natalia N., Bondy-Denomy, Joseph, Wrighton, Kelly C., Woyke, Tanja, Visel, Axel, Kyrpides, Nikos C., and Eloe-Fadrosh, Emiley A. Mon . "Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes". United States. doi:10.1038/s41564-019-0510-x. https://www.osti.gov/servlets/purl/1581331.
@article{osti_1581331,
title = {Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes},
author = {Roux, Simon and Krupovic, Mart and Daly, Rebecca A. and Borges, Adair L. and Nayfach, Stephen and Schulz, Frederik and Sharrar, Allison and Matheus Carnevali, Paula B. and Cheng, Jan-Fang and Ivanova, Natalia N. and Bondy-Denomy, Joseph and Wrighton, Kelly C. and Woyke, Tanja and Visel, Axel and Kyrpides, Nikos C. and Eloe-Fadrosh, Emiley A.},
abstractNote = {Bacteriophages from the Inoviridae family (inoviruses) are characterized by their unique morphology, genome content and infection cycle. One of the most striking features of inoviruses is their ability to establish a chronic infection whereby the viral genome resides within the cell in either an exclusively episomal state or integrated into the host chromosome and virions are continuously released without killing the host. To date, a relatively small number of inovirus isolates have been extensively studied, either for biotechnological applications, such as phage display, or because of their effect on the toxicity of known bacterial pathogens including Vibrio cholerae and Neisseria meningitidis. Here, we show that the current 56 members of the Inoviridae family represent a minute fraction of a highly diverse group of inoviruses. Using a machine learning approach leveraging a combination of marker gene and genome features, we identified 10,295 inovirus-like sequences from microbial genomes and metagenomes. Collectively, our results call for reclassification of the current Inoviridae family into a viral order including six distinct proposed families associated with nearly all bacterial phyla across virtually every ecosystem. Putative inoviruses were also detected in several archaeal genomes, suggesting that, collectively, members of this supergroup infect hosts across the domains Bacteria and Archaea. Finally, we identified an expansive diversity of inovirus-encoded toxin–antitoxin and gene expression modulation systems, alongside evidence of both synergistic (CRISPR evasion) and antagonistic (superinfection exclusion) interactions with co-infecting viruses, which we experimentally validated in a Pseudomonas model. Capturing this previously obscured component of the global virosphere may spark new avenues for microbial manipulation approaches and innovative biotechnological applications.},
doi = {10.1038/s41564-019-0510-x},
journal = {Nature Microbiology},
number = [11],
volume = [4],
place = {United States},
year = {2019},
month = {7}
}

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Cited by: 9 works
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    • Bradbury, Andrew R. M.; Marks, James D.
    • Journal of Immunological Methods, Vol. 290, Issue 1-2
    • DOI: 10.1016/j.jim.2004.04.007

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    journal, November 2003


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    • Oberortner, Ernst; Cheng, Jan-Fang; Hillson, Nathan J.
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    • Rice, Scott A.; Tan, Chuan Hao; Mikkelsen, Per Jensen
    • The ISME Journal, Vol. 3, Issue 3
    • DOI: 10.1038/ismej.2008.109

    CRISPR-Cas immunity in prokaryotes
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    • Paez-Espino, David; Eloe-Fadrosh, Emiley A.; Pavlopoulos, Georgios A.
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    Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs
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    • Eloe-Fadrosh, Emiley A.; Paez-Espino, David; Jarett, Jessica
    • Nature Communications, Vol. 7, Issue 1
    • DOI: 10.1038/ncomms10476

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    • Petersen, Thomas Nordahl; Brunak, Søren; von Heijne, Gunnar
    • Nature Methods, Vol. 8, Issue 10
    • DOI: 10.1038/nmeth.1701

    HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment
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    • Remmert, Michael; Biegert, Andreas; Hauser, Andreas
    • Nature Methods, Vol. 9, Issue 2
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    Laboratory procedures to generate viral metagenomes
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    • Thurber, Rebecca V.; Haynes, Matthew; Breitbart, Mya
    • Nature Protocols, Vol. 4, Issue 4
    • DOI: 10.1038/nprot.2009.10

    The Phyre2 web portal for protein modeling, prediction and analysis
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    • Kelley, Lawrence A.; Mezulis, Stefans; Yates, Christopher M.
    • Nature Protocols, Vol. 10, Issue 6
    • DOI: 10.1038/nprot.2015.053

    Nontargeted virus sequence discovery pipeline and virus clustering for metagenomic data
    journal, July 2017

    • Paez-Espino, David; Pavlopoulos, Georgios A.; Ivanova, Natalia N.
    • Nature Protocols, Vol. 12, Issue 8
    • DOI: 10.1038/nprot.2017.063

    The enigmatic archaeal virosphere
    journal, November 2017

    • Prangishvili, David; Bamford, Dennis H.; Forterre, Patrick
    • Nature Reviews Microbiology, Vol. 15, Issue 12
    • DOI: 10.1038/nrmicro.2017.125

    Rising to the challenge: accelerated pace of discovery transforms marine virology
    journal, February 2015

    • Brum, Jennifer R.; Sullivan, Matthew B.
    • Nature Reviews Microbiology, Vol. 13, Issue 3
    • DOI: 10.1038/nrmicro3404

    An updated evolutionary classification of CRISPR–Cas systems
    journal, September 2015

    • Makarova, Kira S.; Wolf, Yuri I.; Alkhnbashi, Omer S.
    • Nature Reviews Microbiology, Vol. 13, Issue 11, p. 722-736
    • DOI: 10.1038/nrmicro3569

    Recovery of nearly 8,000 metagenome-assembled genomes substantially expands the tree of life
    journal, September 2017

    • Parks, Donovan H.; Rinke, Christian; Chuvochina, Maria
    • Nature Microbiology, Vol. 2, Issue 11
    • DOI: 10.1038/s41564-017-0012-7

    Stamped microbattery electrodes based on self-assembled M13 viruses
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    • Nam, K. T.; Wartena, R.; Yoo, P. J.
    • Proceedings of the National Academy of Sciences, Vol. 105, Issue 45
    • DOI: 10.1073/pnas.0711620105

    Drug delivery vectors based on filamentous bacteriophages and phage-mimetic nanoparticles
    journal, January 2017


    The diversity of single stranded DNA viruses
    journal, February 2006


    Identifying bacterial genes and endosymbiont DNA with Glimmer
    journal, January 2007


    Jalview Version 2--a multiple sequence alignment editor and analysis workbench
    journal, January 2009


    trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses
    journal, June 2009


    CD-HIT: accelerated for clustering the next-generation sequencing data
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    ‘Big things in small packages: the genetics of filamentous phage and effects on fitness of their host’
    journal, February 2015

    • Mai-Prochnow, Anne; Hui, Janice Gee Kay; Kjelleberg, Staffan
    • FEMS Microbiology Reviews, Vol. 39, Issue 4
    • DOI: 10.1093/femsre/fuu007

    MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability
    journal, January 2013

    • Katoh, K.; Standley, D. M.
    • Molecular Biology and Evolution, Vol. 30, Issue 4
    • DOI: 10.1093/molbev/mst010

    IQ-TREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies
    journal, November 2014

    • Nguyen, Lam-Tung; Schmidt, Heiko A.; von Haeseler, Arndt
    • Molecular Biology and Evolution, Vol. 32, Issue 1
    • DOI: 10.1093/molbev/msu300

    The COG database: a tool for genome-scale analysis of protein functions and evolution
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