On a Hot Summer Night ….

It’s August, and if you live in Texas like I do it’s the season to sweat. Unfortunately, along with sweat comes odor, particularly in the armpit (the axilla region). Certain hairy regions of the body, such as the armpit and groin, contain apocrine glands whose physiological function in humans remains poorly understood. The apocrine glands are present from birth but are not activated until the hormonal changes at puberty.  These apocrine glands secrete complex biochemicals along the hair follicles where they are released on the surface of the skin. Since the apocrine glands are stimulated by adrenaline their secretions increase in response to fear, pain, stress, anxiety, and other emotional stimuli. Yet these released biochemicals are odorless, and the characteristic “stinky” underarm smell is not inherent in our sweat. Instead, bacteria generate the smell by taking up these released human biomolecules and cleaving them into volatile compounds, particularly the pungent sulfur-containing thioalcohols. Among the prominent bacteria genera colonizing human armpits are Corynebacterium, Cutibacterium, and Staphylococcus, and it is this last family that is most relevant to odor formation.

There are several Staphylococcus species present on human skin with Staphylococcus epidemidis being the most common. Most of these staph organisms are commensals that are part of our normal skin microbiome and do no harm. A second member of this family, Staphylococcus hominis, is commonly found on regions of the body that contain apocrine glands and has been linked to body odor production, but the biochemical mechanisms responsible for odor production had not been identified. A new publication in the journal Scientific Reports confirms that S. hominis is a chief contributor to body odor and identifies the enzyme present in S. hominis that catalyzes the production of the thioalcohols. This thioalcohol-producing enzyme is called a cysteine-thiol lyase (C-T lyase) because it lyses (breaks) the chemical bond between the cysteine (an amino acid) and the thiol group in the compounds secreted by our apocrine glands. The released thioalcohols are much more volatile than the original secreted compounds and give rise to the acrid, skunky smell of armpit sweat.

Surprisingly, this C-T lyase is limited to only a small subset of Staphylococci, suggesting that the gene for this enzyme is not indigenous to Staphylococcus and was likely acquired from another bacterium. Examination of structurally related enzymes in other bacteria found the closest relative in Bacillus subtilis. B. subtilis is found in the soil but is also present in the human gastrointestinal tract, making it the likely source of the C-T lyase in S. hominis through a process known as horizontal gene transfer (HGT). In HGT, fragments of DNA are randomly transferred from one bacterium to another, and if the transferred fragment contains a gene then the recipient bacterium has acquired new functional genetic information. Comparison of the S. hominis genome with the genomes of Staphylococci lacking the C-T lyase suggests that this gene was acquired at least 60 million years ago before Homo sapiens emerged from our primate forebears. This ancient origin for the C-T lyase gene in S. hominis raises some intriguing unanswered questions that highlight the complex relationship between humans and their microbiome. We know that S. epidemidis is also prevalent in armpits yet it has no C-T lyase, so this enzyme is not essential for staph growth and survival in this location. Why then did this gene persist in S. hominis instead of being lost over time? Did having the C-T lyase give some benefit to this organism that allowed it to thrive in primate apocrine gland locations and become part of our normal flora as humans evolved? Conversely, does S. hominis play any beneficial role for us? Did having smelly bodies provide a survival advantage for primates and early humans that led to selection for individuals who maintained C-T expressing S. hominis as part of their flora? Is deodorant used today because once upon a time being smelly helped us survive or is this odor just an unfortunate side effect of S. hominis finding a nice niche in our armpits? Either way, can we find a safe C-T lyase inhibitor that would eliminate thiol stench once and for all? I’ll stop there and let you think hard about these issues, but don’t work up a sweat!

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