Trace amines produced by skin bacteria accelerate wound healing in mice

Dewi Hidayati,Muhammad Zainul Muttaqin,Kay Nieselt,Friedrich Götz,Arif Luqman,Patrick Ebner,Sumah Yulaipi,Susanne Zabel,Miki Matsuo,Paula Maria Tribelli

doi:10.1038/s42003-020-1000-7

Abstract

Certain skin bacteria are able to convert aromatic amino acids (AAA) into trace amines (TA) that act as neuromodulators. Since the human skin and sweat contain a comparatively high content of AAA one can expect that such bacteria are able to produce TA on our skin. Here we show that TA-producing Staphylococcus epidermidis strains expressing SadA are predominant on human skin and that TA accelerate wound healing. In wounded skin, keratinocytes produce epinephrine (EPI) that leads to cell motility inhibition by β2-adrenergic receptor (β2-AR) activation thus delay wound healing. As β2-AR antagonists, TA and dopamine (DOP) abrogate the effect of EPI thus accelerating wound healing both in vitro and in a mouse model. In the mouse model, the S. epidermidis wild type strain accelerates wound healing compared to its ΔsadA mutant. Our study demonstrates that TA-producing S. epidermidis strains present on our skin might be beneficial for wound healing.

Highlights

Certain skin bacteria are able to convert aromatic amino acids (AAA) into trace amines (TA) that act as neuromodulators
TA-producing Staphylococcus epidermidis strains are predominant on human skin
Since TA-producing staphylococci have an advantage in host cell adherence and internalization[8], we investigated whether and how many TA-producing staphylococci colonize the human skin and its prevalence

Summary

Introduction

Certain skin bacteria are able to convert aromatic amino acids (AAA) into trace amines (TA) that act as neuromodulators. We show that TA-producing Staphylococcus epidermidis strains expressing SadA are predominant on human skin and that TA accelerate wound healing. SadA is highly promiscuous because it decarboxylates all biogenic AAAs into tryptamine (TRY), PEA, and TYM and dihydroxy phenylalanine (L-DOPA) and 5hydroxytryptophan (5-HTP) to the neurotransmitter dopamine (DOP) and serotonin (SER). It was not clear what might be the advantage to the bacteria of having SadA. TA ad DOP activate α2-AR and induce a reduction of the cytoplasmic cAMP level as well as an increased F-actin formation This causes an increased internalization of the bacteria by the host cells. In the meantime it emerged that neurotransmitters and neuromodulators are produced by the host, and by the gut microbiota and that they play a role in the Gut-Brain axis[21]

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Conclusion