Structural assembly of the bacterial essential interactome

  1. Jordi Gomez Borrego
  2. Marc Torrent  Is a corresponding author
  1. Autonomous University of Barcelona, Spain

Abstract

The study of protein interactions in living organisms is fundamental for understanding biological processes and central metabolic pathways. Yet, our knowledge of the bacterial interactome remains limited. Here, we combined gene deletion mutant analysis with deep learning protein folding using Alphafold2 to predict the core bacterial essential interactome. We predicted and modeled 1402 interactions between essential proteins in bacteria and generated 146 high-accuracy models. Our analysis reveals previously unknown details about the assembly mechanisms of these complexes, highlighting the importance of specific structural features in their stability and function. Our work provides a framework for predicting the essential interactomes of bacteria and highlight the potential of deep learning algorithms in advancing our understanding of the complex biology of living organisms. Also, the results presented here offer a promising approach to identify novel antibiotic targets.

Data availability

All models described in this paper are available on ModelArchive (https://modelarchive.org) with accession codes in Table 1. The scores of selected and random binary PPIs and the annotations of the essential proteins are provided in Source data 1.

Article and author information

Author details

  1. Jordi Gomez Borrego

    Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Cerdanyola del Valles, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Marc Torrent

    Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, Cerdanyola del Valles, Spain
    For correspondence
    marc.torrent@uab.cat
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6567-3474

Funding

Ministerio de Ciencia e Innovación (PDC2021-121544-I00)

  • Marc Torrent

Ministerio de Ciencia e Innovación (PDC2021-121544-I00)

  • Marc Torrent

European Society of Clinical Microbiology and Infectious Diseases (ESCMID2022)

  • Marc Torrent

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2024, Gomez Borrego & Torrent

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 351
    downloads

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Jordi Gomez Borrego
  2. Marc Torrent
(2024)
Structural assembly of the bacterial essential interactome
eLife 13:e94919.
https://doi.org/10.7554/eLife.94919

Share this article

https://doi.org/10.7554/eLife.94919

Further reading

    1. Computational and Systems Biology
    2. Neuroscience
    Cesare V Parise, Marc O Ernst
    Research Article

    Audiovisual information reaches the brain via both sustained and transient input channels, representing signals’ intensity over time or changes thereof, respectively. To date, it is unclear to what extent transient and sustained input channels contribute to the combined percept obtained through multisensory integration. Based on the results of two novel psychophysical experiments, here we demonstrate the importance of the transient (instead of the sustained) channel for the integration of audiovisual signals. To account for the present results, we developed a biologically inspired, general-purpose model for multisensory integration, the multisensory correlation detectors, which combines correlated input from unimodal transient channels. Besides accounting for the results of our psychophysical experiments, this model could quantitatively replicate several recent findings in multisensory research, as tested against a large collection of published datasets. In particular, the model could simultaneously account for the perceived timing of audiovisual events, multisensory facilitation in detection tasks, causality judgments, and optimal integration. This study demonstrates that several phenomena in multisensory research that were previously considered unrelated, all stem from the integration of correlated input from unimodal transient channels.

    1. Computational and Systems Biology
    Franck Simon, Maria Colomba Comes ... Herve Isambert
    Tools and Resources

    Live-cell microscopy routinely provides massive amounts of time-lapse images of complex cellular systems under various physiological or therapeutic conditions. However, this wealth of data remains difficult to interpret in terms of causal effects. Here, we describe CausalXtract, a flexible computational pipeline that discovers causal and possibly time-lagged effects from morphodynamic features and cell–cell interactions in live-cell imaging data. CausalXtract methodology combines network-based and information-based frameworks, which is shown to discover causal effects overlooked by classical Granger and Schreiber causality approaches. We showcase the use of CausalXtract to uncover novel causal effects in a tumor-on-chip cellular ecosystem under therapeutically relevant conditions. In particular, we find that cancer-associated fibroblasts directly inhibit cancer cell apoptosis, independently from anticancer treatment. CausalXtract uncovers also multiple antagonistic effects at different time delays. Hence, CausalXtract provides a unique computational tool to interpret live-cell imaging data for a range of fundamental and translational research applications.