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.

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

  • 11,706
    views
  • 1,270
    downloads
  • 35
    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. Genetics and Genomics
    2. Microbiology and Infectious Disease
    Teresa Attenborough, Kate A Rawlinson ... Matthew Berriman
    Research Article

    Schistosoma mansoni is a parasitic flatworm that causes the major neglected tropical disease schistosomiasis. The miracidium is the first larval stage of the life cycle. It swims and infects a freshwater snail, transforms into a mother sporocyst, where its stem cells generate daughter sporocysts that give rise to human-infective cercariae larvae. To understand the miracidium at cellular and molecular levels, we created a whole-body atlas of its ~365 cells. Single-cell RNA sequencing identified 19 transcriptionally distinct cell clusters. In situ hybridisation of tissue-specific genes revealed that 93% of the cells in the larva are somatic (57% neural, 19% muscle, 13% epidermal or tegument, 2% parenchyma, and 2% protonephridia) and 7% are stem. Whereas neurons represent the most diverse somatic cell types, trajectory analysis of the two main stem cell populations indicates that one of them is the origin of the tegument lineage and the other likely contains pluripotent cells. Furthermore, unlike the somatic cells, each of these stem populations shows sex-biased transcriptional signatures suggesting a cell-type-specific gene dosage compensation for sex chromosome-linked loci. The miracidium represents a simple developmental stage with which to gain a fundamental understanding of the molecular biology and spatial architecture of schistosome cells.

    1. Genetics and Genomics
    2. Microbiology and Infectious Disease
    Jessica Gray, Von Vergel L Torres ... Ian R Henderson
    Research Article

    Klebsiella pneumoniae is a global public health concern due to the rising myriad of hypervirulent and multidrug-resistant clones both alarmingly associated with high mortality. The molecular mechanisms underpinning these recalcitrant K. pneumoniae infection, and how virulence is coupled with the emergence of lineages resistant to nearly all present-day clinically important antimicrobials, are unclear. In this study, we performed a genome-wide screen in K. pneumoniae ECL8, a member of the endemic K2-ST375 pathotype most often reported in Asia, to define genes essential for growth in a nutrient-rich laboratory medium (Luria-Bertani [LB] medium), human urine, and serum. Through transposon directed insertion-site sequencing (TraDIS), a total of 427 genes were identified as essential for growth on LB agar, whereas transposon insertions in 11 and 144 genes decreased fitness for growth in either urine or serum, respectively. These studies not only provide further knowledge on the genetics of this pathogen but also provide a strong impetus for discovering new antimicrobial targets to improve current therapeutic options for K. pneumoniae infections.