1. Microbiology and Infectious Disease
  2. Structural Biology and Molecular Biophysics
Download icon

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
Research Article
  • Cited 19
  • Views 9,332
  • Annotations
Cite this article as: eLife 2018;7:e34995 doi: 10.7554/eLife.34995

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

Publication 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

  • 9,332
    Page views
  • 1,058
    Downloads
  • 19
    Citations

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

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)

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

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

Categories and tags

Research organism

Further reading

    1. Microbiology and Infectious Disease

    In situ imaging of bacterial outer membrane projections and associated protein complexes using electron cryo-tomography

    Mohammed Kaplan et al.
    Research Article Updated

    The ability to produce outer membrane projections in the form of tubular membrane extensions (MEs) and membrane vesicles (MVs) is a widespread phenomenon among diderm bacteria. Despite this, our knowledge of the ultrastructure of these extensions and their associated protein complexes remains limited. Here, we surveyed the ultrastructure and formation of MEs and MVs, and their associated protein complexes, in tens of thousands of electron cryo-tomograms of ~90 bacterial species that we have collected for various projects over the past 15 years (Jensen lab database), in addition to data generated in the Briegel lab. We identified outer MEs and MVs in 13 diderm bacterial species and classified several major ultrastructures: (1) tubes with a uniform diameter (with or without an internal scaffold), (2) tubes with irregular diameter, (3) tubes with a vesicular dilation at their tip, (4) pearling tubes, (5) connected chains of vesicles (with or without neck-like connectors), (6) budding vesicles and nanopods. We also identified several protein complexes associated with these MEs and MVs which were distributed either randomly or exclusively at the tip. These complexes include a secretin-like structure and a novel crown-shaped structure observed primarily in vesicles from lysed cells. In total, this work helps to characterize the diversity of bacterial membrane projections and lays the groundwork for future research in this field.

    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Vaccination induces rapid protection against bacterial pneumonia via training alveolar macrophage in mice

    Hao Gu et al.
    Research Article

    Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.

    1. Microbiology and Infectious Disease

    Unexpected plasticity in the life cycle of Trypanosoma brucei

    Sarah Schuster et al.
    Research Article Updated

    African trypanosomes cause sleeping sickness in humans and nagana in cattle. These unicellular parasites are transmitted by the bloodsucking tsetse fly. In the mammalian host’s circulation, proliferating slender stage cells differentiate into cell cycle-arrested stumpy stage cells when they reach high population densities. This stage transition is thought to fulfil two main functions: first, it auto-regulates the parasite load in the host; second, the stumpy stage is regarded as the only stage capable of successful vector transmission. Here, we show that proliferating slender stage trypanosomes express the mRNA and protein of a known stumpy stage marker, complete the complex life cycle in the fly as successfully as the stumpy stage, and require only a single parasite for productive infection. These findings suggest a reassessment of the traditional view of the trypanosome life cycle. They may also provide a solution to a long-lasting paradox, namely the successful transmission of parasites in chronic infections, despite low parasitemia.