The generation of malodour on various sites of the human body is caused by the microbial biotransformation of odourless natural secretions into volatile odorous molecules. On the skin surface, distinctive odours emanate, in particular, from the underarm (axilla), where a large and permanent population of microorganisms thrives on secretions from the eccrine, apocrine and sebaceous glands. Traditional culture-based microbiological studies inform us that this resident microbiota consists mainly of Gram-positive bacteria of the genera Staphylococcus, Micrococcus, Corynebacterium and Propionibacterium. Among the molecular classes that have been implicated in axillary malodour are short- and medium-chain volatile fatty acids, 16-androstene steroids and, most recently, thioalcohols. Most of the available evidence suggests that members of the Corynebacterium genus are the primary causal agents of axillary odour, with the key malodour substrates believed to originate from the apocrine gland. In this article, we examine, in detail, the microbiology and biochemistry of malodour formation on axillary skin, focussing on precursor-product relationships, odour-forming enzymes and metabolic pathways and causal organisms. As well as reviewing the literature, some relevant new data are presented and considered alongside that already available in the public domain to reach an informed view on the current state-of-the-art, as well as future perspectives.

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...

Although foot malodour is a common consumer problem, the range of products available to combat the condition is fairly limited. In part, this is due to an incomplete understanding of how the key odorants are generated by microorganisms resident on the skin. The aim of these studies was to identify the key chemical components of foot malodour, the organisms and metabolic pathways responsible for their production, and to develop model systems to study these processes in vitro. Using gas chromatography with simultaneous mass spectrometry and sniff port detection, volatile fatty acids were implicated as foot malodorants, with isovaleric acid particularly prominent. l‐Leucine was identified as the likely substrate, and the source of this branched amino acid postulated to be the degradation of foot callus. An in vitro assay was employed to screen a library of isolated foot bacteria for their ability to generate isovaleric acid from l‐leucine. Staphylococcus species were found to be the main producers, while some Brevibacterium, Micrococcus and Kytococcus isolates fully catabolized isovaleric acid and l‐leucine, indicating the dynamic nature of odour production. The degradation of foot callus by Kytococcus sedentarius was investigated, and an in vitro ‘foot malodour model’ developed, demonstrating the generation of isovaleric acid using a combination of partially purified K. sedentarius keratinases and a Staphylococcus species. The results of these studies provide new understanding on the microbiological and biochemical origins of foot malodour which, in turn, should lead to the development of novel deodorant systems for this part of the body. Copyright © 2012 John Wiley & Sons, Ltd.

Dandruff is a global consumer problem, characterized by flaking and scaling of the scalp, accompanied by itch and irritancy. However, the aetiology of the condition remains poorly understood, although there is a strong consensus that the cutaneous fungi Malassezia globosa and M. restricta are a major contributory factor. Although there is a paucity of understanding on how these commensal microorganisms adopt a pathogenic phenotype, a rich source of potential insights now exists in the shape of the recently published whole-genome sequence of M. globosa, a functional annotation and metabolic reconstruction of which is freely accessible via the integrated microbial genomes (IMG) online community resource (http://www.hmpdacc-resources.org/cgi-bin/imgm_hmp/main.cgi). In these studies, we have taken a combined in-silico and in-vitro approach to investigate aspects of lipid and amino acid metabolism by M. globosa and M. restricta that have the potential to impact on scalp condition and dandruff. The IMG platform was employed to analyse the metabolism of triacylglycerols and fatty acids, as well as the aromatic amino acid tryptophan, by M. globosa, to investigate pro-inflammatory pathways linked in the literature to dandruff and pityriasis versicolour, respectively. Results were equivocal, leaving question marks over the ability of M. globosa to fully degrade unsaturated fatty acids and metabolize tryptophan to indole-3-pyruvic acid. In-vitro assay systems were then developed to study the biotransformation of these metabolites by both M. globosa and M. restricta, as well as their effect on human keratinocytes, and the results here indicated that neither unsaturated fatty acids nor indole derivatives are likely to be major aetiological factors in dandruff.