Nanoscale resolution of microbial fiber degradation in action

  1. Meltem Tatli
  2. Sarah Moraïs
  3. Omar E Tovar-Herrera
  4. Yannick J Bomble
  5. Edward A Bayer
  6. Ohad Medalia  Is a corresponding author
  7. Itzhak Mizrahi  Is a corresponding author
  1. University of Zurich, Switzerland
  2. Ben-Gurion University of the Negev, Israel
  3. National Renewable Energy Laboratory, United States
  4. Weizmann Institute of Science, Israel
  5. University of Zürich, Switzerland

Abstract

The lives of microbes unfold at the micron scale, and their molecular machineries operate at the nanoscale. Their study at these resolutions is key towards achieving a better understanding of their ecology. We focus on cellulose degradation of the canonical Clostridium thermocellum system to comprehend how microbes build and use their cellulosomal machinery at these nanometer scales. Degradation of cellulose, the most abundant organic polymer on Earth, is instrumental to the global carbon cycle. We reveal that bacterial cells form 'cellulosome capsules' driven by catalytic product-dependent dynamics, which can increase the rate of hydrolysis. Biosynthesis of this energetically costly machinery and cell growth are decoupled at the single-cell level, hinting at a division-of-labor strategy through phenotypic heterogeneity. This novel observation highlights intra-population interactions as key to understanding rates of fiber degradation.

Data availability

Structural data that support the findings of this study has been deposited in the Electron Microscopy Data Bank https://www.ebi.ac.uk/emdb/ (accession code EMD-11986). Representative data set can be found in EMPIAR under the accession number EMPIAR-10593.

The following data sets were generated

Article and author information

Author details

  1. Meltem Tatli

    Department of Biochemistry, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Sarah Moraïs

    Faculty of Natural Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Omar E Tovar-Herrera

    Faculty of Natural Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Yannick J Bomble

    National Renewable Energy Laboratory, Golden, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7624-8000
  5. Edward A Bayer

    Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Ohad Medalia

    Department of Biochemistry, University of Zürich, Zurich, Switzerland
    For correspondence
    omedalia@bioc.uzh.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0994-2937
  7. Itzhak Mizrahi

    Faculty of Natural Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
    For correspondence
    imizrahi@bgu.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6636-8818

Funding

Deutsche Forschungsgemeinschaft (2476/2 -1)

  • Ohad Medalia
  • Itzhak Mizrahi

HORIZON EUROPE European Research Council (64084)

  • Itzhak Mizrahi

Swiss national foundation (31003A_179418)

  • Ohad Medalia

Center for Bioenergy Innovation

  • Yannick J Bomble

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

Reviewing Editor

  1. Steven Smith

Version history

  1. Preprint posted: February 16, 2021 (view preprint)
  2. Received: December 21, 2021
  3. Accepted: May 30, 2022
  4. Accepted Manuscript published: May 31, 2022 (version 1)
  5. Version of Record published: June 13, 2022 (version 2)
  6. Version of Record updated: June 21, 2022 (version 3)

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

  • 1,251
    Page views
  • 320
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, 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. Meltem Tatli
  2. Sarah Moraïs
  3. Omar E Tovar-Herrera
  4. Yannick J Bomble
  5. Edward A Bayer
  6. Ohad Medalia
  7. Itzhak Mizrahi
(2022)
Nanoscale resolution of microbial fiber degradation in action
eLife 11:e76523.
https://doi.org/10.7554/eLife.76523

Share this article

https://doi.org/10.7554/eLife.76523

Further reading

    1. Microbiology and Infectious Disease
    Nguyen Thi Khanh Nhu, Minh-Duy Phan ... Mark A Schembri
    Research Article

    Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974–2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.

    1. Microbiology and Infectious Disease
    Swati Jain, Gherman Uritskiy ... Venigalla B Rao
    Research Article

    A productive HIV-1 infection in humans is often established by transmission and propagation of a single transmitted/founder (T/F) virus, which then evolves into a complex mixture of variants during the lifetime of infection. An effective HIV-1 vaccine should elicit broad immune responses in order to block the entry of diverse T/F viruses. Currently, no such vaccine exists. An in-depth study of escape variants emerging under host immune pressure during very early stages of infection might provide insights into such a HIV-1 vaccine design. Here, in a rare longitudinal study involving HIV-1 infected individuals just days after infection in the absence of antiretroviral therapy, we discovered a remarkable genetic shift that resulted in near complete disappearance of the original T/F virus and appearance of a variant with H173Y mutation in the variable V2 domain of the HIV-1 envelope protein. This coincided with the disappearance of the first wave of strictly H173-specific antibodies and emergence of a second wave of Y173-specific antibodies with increased breadth. Structural analyses indicated conformational dynamism of the envelope protein which likely allowed selection of escape variants with a conformational switch in the V2 domain from an α-helix (H173) to a β-strand (Y173) and induction of broadly reactive antibody responses. This differential breadth due to a single mutational change was also recapitulated in a mouse model. Rationally designed combinatorial libraries containing 54 conformational variants of V2 domain around position 173 further demonstrated increased breadth of antibody responses elicited to diverse HIV-1 envelope proteins. These results offer new insights into designing broadly effective HIV-1 vaccines.