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.

Background: Haemophilus influenzae requires a substrate-binding protein (SBP)-dependent TRAP transporter to acquire sialic acid.Results: A conserved arginine residue in the SBP is essential for the high affinity and carboxylate specificity of the TRAP transporter.Conclusion: The arginine/carboxylate interaction in TRAP SBPs restricts substrate range to carboxylate-containing substrates.Significance: The study reveals the mechanism by which a key bimolecular interaction underpins bacterial virulence.

The production of malodour by humans is mediated by bacterial transformation of naturally secreted, non-odorous molecules. Specifically in the underarm (axilla), malodour arises due to biotransformation by the microbiota of dipeptide-conjugated thioalcohols, particularly S-[1-(2-hydroxyethyl)-1-methylbutyl]-(L)-cysteinylglycine (Cys-Gly-3M3SH). This molecule, secreted by the axilla, has a well-established role in malodour when metabolized to free thioalcohol by bacteria. We present Cys-Gly-3M3SH biotransformation data from a library of skin-isolated corynebacteria and staphylococci and report a significant variation in thioalcohol generation across individual bacterial species. Staphylococcus hominis, Staphylococcus haemolyticus and Staphylococcus lugdunensis were particularly efficient Cys-Gly-3M3SH transformers. In contrast, Staphylococcus epidermidis and Corynebacterium tuberculostearicum, both highly prevalent axillary commensals, are low producers of 3M3SH. We also identify significant differences between the ability of several isolates to biotransform Cys-Gly-3M3SH compared to S-benzyl-L-Cys-Gly, a dipeptide-linked version of a commonly used malodour precursor substrate. Finally, using traditional biochemical assays we subsequently establish that Cys-Gly-3M3SH is actively transported into S. hominis, rather than passively diffusing across the membrane. This work significantly enhances our knowledge of Cys-Gly-3M3SH biotransformation by physiologically important bacteria in the axillary microbiota.

Body odour is a characteristic trait of Homo sapiens, however its role in human behaviour and evolution is poorly understood. Remarkably, body odour is linked to the presence of a few species of commensal microbes. Herein we discover a bacterial enzyme, limited to odour-forming staphylococci that are able to cleave odourless precursors of thioalcohols, the most pungent components of body odour. We demonstrated using phylogenetics, biochemistry and structural biology that this cysteinethiol lyase (C-T lyase) is a PLP-dependent enzyme that moved horizontally into a unique monophyletic group of odour-forming staphylococci about 60 million years ago, and has subsequently tailored its enzymatic function to human-derived thioalcohol precursors. Significantly, transfer of this enzyme alone to non-odour producing staphylococci confers odour production, demonstrating that this C-T lyase is both necessary and sufficient for thioalcohol formation. The structure of the C-T lyase compared to that of other related enzymes reveals how the adaptation to thioalcohol precursors has evolved through changes in the binding site to create a constrained hydrophobic pocket that is selective for branched aliphatic thioalcohol ligands. The ancestral acquisition of this enzyme, and the subsequent evolution of the specificity for thioalcohol precursors implies that body odour production in humans is an ancient process. Human body odour is produced by bacterial transformation of odourless precursor molecules secreted onto the surface of the skin by apocrine glands 1-3. These glands are one of two major types of sweat gland found in Homo sapiens, the other being the eccrine glands. Eccrine glands are found in high density all over the body, they open directly onto the surface of the skin and are essential for thermoregulation 4 (Fig. 1A). In contrast, apocrine glands open into hair follicles and typically occur in high density at specific body sites (axilla [underarm], nipple and external genitalia) (Fig. 1A); their exact function and physiological role in modern humans remain poorly understood. The axillary microbiota plays an important role in the generation of human body odour. Staphylococcus, Cutibacterium (formerly Propionibacterium) and Corynebacterium are the dominant genera colonizing the axilla 5,6 , with recent metataxonomic studies highlighting the additional presence of Gram-positive anaerobic cocci (GPAC), notably Anaerococcus and Peptoniphilus species 5,7. Human axillary malodour is comprised of a mixture of volatile organic compounds with volatile fatty acids (VFAs) and thioalcohols being the primary components (Supplementary Information Figure S1) 8-10. Thioalcohols, despite being present in trace amounts, are the most pungent voaltiles 9. Natsch et al. 2,11 identified trace amounts of four different thioalcohols in axillary secretions with 3-methyl-3-sulfanylhexan-1-ol (3M3SH) being the most abundant. 3M3SH is generated from the odourless precursor Cys-Gly-3M3SH, an l-cysteinylglycine dipeptide-conjugated alcohol that is secr...

No abstract