Interaction of skin-born mediators with the cutaneous microbiota and beyond

Cutaneous microorganisms are growing in a microenvironment where skin hormones and neurohormones are present in abundance. These molecules are markers of the host physiology, and microorganisms have developed strategies for detecting host factors that can represent a threat for their survival. Until now, our knowledge of these mechanisms is limited to bacteria, although the skin microbiota also includes an abundance of yeasts, fungi, viruses, and even archaea. Several human hormones and neurotransmitters, including substance P, calcitonin gene-related peptides, natriuretic peptides, catecholamines, and even estradiol have been studied in this context. This was leading to the identification of original proteins, such as the thermo-unstable ribosomal elongation factor, the chaperone DnaK, or the enzyme AmiC, which have been developed by bacteria and have dual functions, in the cytoplasm where they were originally identified and in the bacterial membrane where they act as sensors for host factors. These sensors, designed as moonlighting proteins for their dual functions, are submitted to structural reorganizations and probably post-translational modifications. The occurrence of epigenetic mechanisms in the regulation of moonlighting proteins activity is a source of major complications since similar processes are activated during bacteria adaptation to the host physiology and even storage. Cutaneous bacterial endocrinology is a wide and complex emerging scientific field that requires a deep knowledge of both human and microbial physiology and careful experimental procedures.