Bacterial Death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans

  1. Gurmeet Kaur
  2. Lakshminarayan M Iyer
  3. A Maxwell Burroughs
  4. L Aravind  Is a corresponding author
  1. National Institutes of Health, United States

Abstract

Several homologous domains are shared by eukaryotic immunity and programmed cell-death systems and poorly understood bacterial proteins. Recent studies show these to be components of a network of highly regulated systems connecting apoptotic processes to counter-invader immunity, in prokaryotes with a multicellular habit. However, the provenance of key adaptor domains, namely those of the Death-like and TRADD-N superfamilies, a quintessential feature of metazoan apoptotic systems, remained murky. Here, we use sensitive sequence analysis and comparative genomics methods to identify unambiguous bacterial homologs of the Death-like and TRADD-N superfamilies. We show the former to have arisen as part of a radiation of effector-associated α-helical adaptor domains that likely mediate homotypic interactions bringing together diverse effector and signaling domains in predicted bacterial apoptosis- and counter-invader systems. Similarly, we show that the TRADD-N domain defines a key, widespread signaling bridge that links effector deployment to invader-sensing in multicellular bacterial and metazoan counter-invader systems. TRADD-N domains are expanded in aggregating marine invertebrates and point to distinctive diversifying immune strategies probably directed both at RNA and retro- viruses and cellular pathogens that might infect such communities. These TRADD-N and Death-like domains helped identify several new bacterial and metazoan counter-invader systems featuring under-appreciated, common functional principles: the use of intracellular invader-sensing lectin-like (NPCBM and FGS), transcription elongation GreA/B-C, glycosyltransferase-4 family, inactive NTPase (serving as nucleic-acid-receptors) and invader-sensing GTPase switch domains. Finally, these findings point to the possibility of multicellular bacteria-stem metazoan symbiosis in the emergence of the immune/apoptotic systems of the latter.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 3, 4, 5, 6.

Article and author information

Author details

  1. Gurmeet Kaur

    Computational Biology Branch, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Lakshminarayan M Iyer

    Computational Biology Branch, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. A Maxwell Burroughs

    Computational Biology Branch, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2229-8771
  4. L Aravind

    Computational Biology Branch, National Institutes of Health, Bethesda, United States
    For correspondence
    aravind@mail.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0771-253X

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: May 16, 2021
  2. Accepted: May 23, 2021
  3. Accepted Manuscript published: June 1, 2021 (version 1)
  4. Version of Record published: June 10, 2021 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 976
    Page views
  • 194
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Gurmeet Kaur
  2. Lakshminarayan M Iyer
  3. A Maxwell Burroughs
  4. L Aravind
(2021)
Bacterial Death and TRADD-N domains help define novel apoptosis and immunity mechanisms shared by prokaryotes and metazoans
eLife 10:e70394.
https://doi.org/10.7554/eLife.70394

Further reading

    1. Computational and Systems Biology
    Zhuang Liu et al.
    Research Article

    MicroRNAs (miR), as important epigenetic control factors, reportedly regulate wound repair. However, our insufficient knowledge of clinically relevant miRs hinders their potential therapeutic use. For this, we performed paired small RNA and long RNA sequencing and integrative omics analysis in human tissue samples, including matched skin and acute wounds collected at each healing stage and chronic non-healing venous ulcers (VU). On the basis of the findings, we developed a compendium (https://www.xulandenlab.com/humanwounds-mirna-mrna), which will be an open, comprehensive resource to broadly aid wound healing research. With this first clinical, wound-centric resource of miRs and mRNAs, we identified 17 pathologically relevant miRs that exhibited abnormal VU expression and displayed their targets enriched explicitly in the VU gene signature. Intermeshing regulatory networks controlled by these miRs revealed their high cooperativity in contributing to chronic wound pathology characterized by persistent inflammation and proliferative phase initiation failure. Furthermore, we demonstrated that miR-34a, miR-424, and miR-516, upregulated in VU, cooperatively suppressed keratinocyte migration and growth while promoting inflammatory response. By combining miR expression patterns with their specific target gene expression context, we identified miRs highly relevant to VU pathology. Our study opens the possibility of developing innovative wound treatment that targets pathologically relevant cooperating miRs to attain higher therapeutic efficacy and specificity.

    1. Computational and Systems Biology
    2. Neuroscience
    Emmanuelle Bioud et al.
    Research Article

    To decide whether a course of action is worth pursuing, individuals typically weigh its expected costs and benefits. Optimal decision-making relies upon accurate effort cost anticipation, which is generally assumed to be performed independently from goal valuation. In two experiments (n = 46), we challenged this independence principle of standard decision theory. We presented participants with a series of treadmill routes randomly associated to monetary rewards and collected both ‘accept’ versus ‘decline’ decisions and subjective estimates of energetic cost. Behavioural results show that higher monetary prospects led participants to provide higher cost estimates, although reward was independent from effort in our design. Among candidate cognitive explanations, they support a model in which prospective cost assessment is biased by the output of an automatic computation adjusting effort expenditure to goal value. This decision bias might lead people to abandon the pursuit of valuable goals that are in fact not so costly to achieve.