Structural basis of malodour precursor transport in the human axilla

  1. Gurdeep S Minhas
  2. Daniel Bawdon
  3. Reyme Herman
  4. Michelle Rudden
  5. Andrew P Stone
  6. A Gordon James
  7. Gavin H Thomas  Is a corresponding author
  8. Simon Newstead  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. University of York, United Kingdom
  3. Unilever Discover, United Kingdom

Abstract

Mammals produce volatile odours that convey different types of societal information. In Homo sapiens, this is now recognised as body odour, a key chemical component of which is the sulphurous thioalcohol, 3-methyl-3-sulfanylhexan-1-ol (3M3SH). Volatile 3M3SH is produced in the underarm as a result of specific microbial activity, which act on the odourless dipeptide-containing malodour precursor molecule, S-Cys-Gly-3M3SH, secreted in the axilla (underarm) during colonisation. The mechanism by which these bacteria recognise S-Cys-Gly-3M3SH and produce body odour is still poorly understood. Here we report the structural and biochemical basis of bacterial transport of S-Cys-Gly-3M3SH by Staphylococcus hominis, which is converted to the sulphurous thioalcohol component 3M3SH in the bacterial cytoplasm, before being released into the environment. Knowledge of the molecular basis of precursor transport, essential for body odour formation, provides a novel opportunity to design specific inhibitors of malodour production in humans.

Data availability

Diffraction data have been deposited in PDB under the accession code 6EXS.Vectors have been deposited in Addgene.

The following data sets were generated

Article and author information

Author details

  1. Gurdeep S Minhas

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  2. Daniel Bawdon

    Department of Biology, University of York, York, United Kingdom
    Competing interests
    No competing interests declared.
  3. Reyme Herman

    Department of Biology, University of York, York, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6620-3981
  4. Michelle Rudden

    Department of Biology, University of York, York, United Kingdom
    Competing interests
    No competing interests declared.
  5. Andrew P Stone

    Department of Biology, University of York, York, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1087-9923
  6. A Gordon James

    Personal Care, Unilever Discover, Bedford, United Kingdom
    Competing interests
    A Gordon James, is affiliated with Unilever Discover. The author has no financial interests to declare.
  7. Gavin H Thomas

    Department of Biology, University of York, York, United Kingdom
    For correspondence
    gavin.thomas@york.ac.uk
    Competing interests
    No competing interests declared.
  8. Simon Newstead

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    simon.newstead@bioch.ox.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7432-2270

Funding

Wellcome (102890/Z/13/Z)

  • Simon Newstead

Biotechnology and Biological Sciences Research Council (BB/N006615/1)

  • Gavin H Thomas

Biotechnology and Biological Sciences Research Council (BB/L013703/1)

  • Gavin H Thomas
  • Simon Newstead

Biotechnology and Biological Sciences Research Council (BB/H016201/1)

  • Daniel Bawdon
  • A Gordon James
  • Gavin H Thomas

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

Reviewing Editor

  1. Olga Boudker, Weill Cornell Medicine, United States

Version history

  1. Received: January 11, 2018
  2. Accepted: June 23, 2018
  3. Accepted Manuscript published: July 3, 2018 (version 1)
  4. Version of Record published: July 25, 2018 (version 2)

Copyright

© 2018, Minhas et al.

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

  • 11,559
    views
  • 1,255
    downloads
  • 33
    citations

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. Gurdeep S Minhas
  2. Daniel Bawdon
  3. Reyme Herman
  4. Michelle Rudden
  5. Andrew P Stone
  6. A Gordon James
  7. Gavin H Thomas
  8. Simon Newstead
(2018)
Structural basis of malodour precursor transport in the human axilla
eLife 7:e34995.
https://doi.org/10.7554/eLife.34995

Share this article

https://doi.org/10.7554/eLife.34995

Further reading

    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease
    Ffion R Hammond, Amy Lewis ... Philip M Elks
    Research Article

    Tuberculosis is a major global health problem and is one of the top 10 causes of death worldwide. There is a pressing need for new treatments that circumvent emerging antibiotic resistance. Mycobacterium tuberculosis parasitises macrophages, reprogramming them to establish a niche in which to proliferate, therefore macrophage manipulation is a potential host-directed therapy if druggable molecular targets could be identified. The pseudokinase Tribbles1 (Trib1) regulates multiple innate immune processes and inflammatory profiles making it a potential drug target in infections. Trib1 controls macrophage function, cytokine production, and macrophage polarisation. Despite wide-ranging effects on leukocyte biology, data exploring the roles of Tribbles in infection in vivo are limited. Here, we identify that human Tribbles1 is expressed in monocytes and is upregulated at the transcript level after stimulation with mycobacterial antigen. To investigate the mechanistic roles of Tribbles in the host response to mycobacteria in vivo, we used a zebrafish Mycobacterium marinum (Mm) infection tuberculosis model. Zebrafish Tribbles family members were characterised and shown to have substantial mRNA and protein sequence homology to their human orthologues. trib1 overexpression was host-protective against Mm infection, reducing burden by approximately 50%. Conversely, trib1 knockdown/knockout exhibited increased infection. Mechanistically, trib1 overexpression significantly increased the levels of proinflammatory factors il-1β and nitric oxide. The host-protective effect of trib1 was found to be dependent on the E3 ubiquitin kinase Cop1. These findings highlight the importance of Trib1 and Cop1 as immune regulators during infection in vivo and suggest that enhancing macrophage TRIB1 levels may provide a tractable therapeutic intervention to improve bacterial infection outcomes in tuberculosis.

    1. Microbiology and Infectious Disease
    2. Physics of Living Systems
    Chi Zhang, Rongjing Zhang, Junhua Yuan
    Research Article

    Bacteria in biofilms secrete potassium ions to attract free swimming cells. However, the basis of chemotaxis to potassium remains poorly understood. Here, using a microfluidic device, we found that Escherichia coli can rapidly accumulate in regions of high potassium concentration on the order of millimoles. Using a bead assay, we measured the dynamic response of individual flagellar motors to stepwise changes in potassium concentration, finding that the response resulted from the chemotaxis signaling pathway. To characterize the chemotactic response to potassium, we measured the dose–response curve and adaptation kinetics via an Förster resonance energy transfer (FRET) assay, finding that the chemotaxis pathway exhibited a sensitive response and fast adaptation to potassium. We further found that the two major chemoreceptors Tar and Tsr respond differently to potassium. Tar receptors exhibit a biphasic response, whereas Tsr receptors respond to potassium as an attractant. These different responses were consistent with the responses of the two receptors to intracellular pH changes. The sensitive response and fast adaptation allow bacteria to sense and localize small changes in potassium concentration. The differential responses of Tar and Tsr receptors to potassium suggest that cells at different growth stages respond differently to potassium and may have different requirements for potassium.