Trace amines produced by skin bacteria accelerate wound healing in mice

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

doi:10.1038/s42003-020-1000-7

Cited by 37 publications

(29 citation statements)

References 67 publications

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“…This may reinforce the hypothesis that the excreted TA interfere with host communication to improve the survival and colonization of the bacteria (Luqman et al, 2018(Luqman et al, , 2019. More recently it has been shown that TA-producing Staphylococcus epidermidis strains expressing SadA are predominant on human skin and that TA accelerate wound healing by antagonizing the β2-adrenergic receptor (β2-AR) in keratinocytes (Luqman et al, 2020b).…”

Section: Introductionsupporting

confidence: 55%

“…We show that the intestinal (Luqman et al, 2018) and skin microbiota is quite capable of increasing the concentration of TA, and that the increased TA concentration causes new activities and interactions with receptors. It has been shown already that TA interact with α2and β-AR and the biological consequences (Luqman et al, 2018(Luqman et al, , 2019(Luqman et al, , 2020b. But these are probably not the only receptors with which TA interact.…”

Section: Discussionmentioning

confidence: 99%

“…This raises the question whether the endogenous synthesis of TA plays a major role at all, or whether the uptake of TA from food and the production of TA by the microbiota are not as such decisive for exerting effects in mammalians. This assumption is supported by the relatively high concentrations of AAAs and TA present on human skin (10 and 5 µg/100 cm 2 , respectively) (Luqman et al, 2020b). Substantial TA concentrations have also been reported in the human gut in the decreasing order of TYM (from 7.6 to 621 µg g −1 of stool sample, depending on the subject), DOP, TRY, serotonin, and PEA (Luqman et al, 2018).…”

Section: Introductionmentioning

confidence: 91%

“…It decarboxylates all AAAs to TAs, and also dihydroxylated phenylalanine and 5-HTP to the neurotransmitters DOP and serotonin (Luqman et al, 2018). SadA producing staphylococci are prevalent in the gut and the human skin (Luqman et al, 2018(Luqman et al, , 2019(Luqman et al, , 2020b.…”

Section: Introductionmentioning

confidence: 99%

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The Neuromodulator-Encoding sadA Gene Is Widely Distributed in the Human Skin Microbiome

et al. 2020

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Trace amines (TA) are endogenously produced in mammals, have a low concentration in the central nervous system (CNS), but trigger a variety of neurological effects and intervene in host cell communication. It emerged that neurotransmitters and TA are produced also by the microbiota. As it has been shown that TA contribute to wound healing, we examined the skin microbiome of probands using shotgun metagenomics. The phyla Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes were predominant. Since SadA is a highly promiscuous TA-producing decarboxylase in Firmicutes, the skin microbiome was specifically examined for the presence of sadA-homologous genes. By mapping the reads of certain genes, we found that, although there were less reads mapping to sadA than to ubiquitous housekeeping genes (arcC and mutS), normalized reads counts were still >1000 times higher than those of rare control genes (icaA, icaB, and epiA). At protein sequence level SadA homologs were found in at least 7 phyla: Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, Acidobacteria, Chloroflexi, and Cyanobacteria, and in 23 genera of the phylum Firmicutes. A high proportion of the genera that have a SadA homolog belong to the classical skin and intestinal microbiota. The distribution of sadA in so many different phyla illustrates the importance of horizontal gene transfer (HGT). We show that the sadA gene is widely distributed in the human skin microbiome. When comparing the sadA read counts in the probands, there was no correlation between age and gender, but an enormous difference in the sadA read counts in the microbiome of the individuals. Since sadA is involved in TA synthesis, it is likely that the TA content of the skin is correlated with the amount of TA producing bacteria in the microbiome. In this way, the microbiome-generated TA could influence signal transmission in the epithelial and nervous system.

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Section: Introductionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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The Neuromodulator-Encoding sadA Gene Is Widely Distributed in the Human Skin Microbiome

et al. 2020

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“…A more recent example in biofilm studies was the use of O47, along with other S. epidermidis strains to analyze the functions of non-coding RNA rsaE in biofilm communities ( Schoenfelder et al, 2019 ). In our latest findings, it was reported that a majority of skin S. epidermidis isolates express the staphylococcal aromatic amino acid decarboxylase (SadA) which enables the strains to produce trace amines from aromatic amino acids ( Luqman et al, 2020 ). sadA was first described in S. pseudintermedius ED99 ( Luqman et al, 2018 ) and this gene is also found in O47.…”

Section: Discussionmentioning

confidence: 99%

The Genome of Staphylococcus epidermidis O47

et al. 2020

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The skin colonizing coagulase-negative Staphylococcus epidermidis causes nosocomial infections and is an important opportunistic and highly adaptable pathogen. To gain more insight into this species, we sequenced the genome of the biofilm positive, methicillin susceptible S. epidermidis O47 strain (hereafter O47). This strain belongs to the most frequently isolated sequence type 2. In comparison to the RP62A strain, O47 can be transformed, which makes it a preferred strain for molecular studies. S. epidermidis O47's genome has a single chromosome of about 2.5 million base pairs and no plasmid. Its oriC sequence has the same directionality as S. epidermidis RP62A, S. carnosus, S. haemolyticus, S. saprophyticus and is inverted in comparison to Staphylococcus aureus and S. epidermidis ATCC 12228. A phylogenetic analysis based on all S. epidermidis genomes currently available at GenBank revealed that O47 is closest related to DAR1907. The genome of O47 contains genes for the typical global regulatory systems known in staphylococci. In addition, it contains most of the genes encoding for the typical virulence factors for S. epidermidis but not for S. aureus with the exception of a putative hemolysin III. O47 has the typical S. epidermidis genetic islands and several mobile genetic elements, which include staphylococcal cassette chromosome (SCC) of about 54 kb length and two prophages ϕO47A and ϕO47B. However, its genome has no transposons and the smallest number of insertion sequence (IS) elements compared to the other known S. epidermidis genomes. By sequencing and analyzing the genome of O47, we provide the basis for its utilization in genetic and molecular studies of biofilm formation.

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Mechanism and application of β‐adrenoceptor blockers in soft tissue wound healing

Jia

Wang

et al. 2023

Medicinal Research Reviews

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Soft tissue damage stimulates sympathetic nerves to release large amounts of catecholamine hormones which bind to β‐adrenergic receptors (β‐ARs) on the cell membrane surface. It activates the downstream effector molecules and impairs soft tissue wound healing. β‐blockers specifically inhibit β‐ARs activation in acute/chronic skin lesions and ulcerative hemangiomas. They also accelerate soft tissue wound healing by shortening the duration of inflammation, speeding keratinocyte migration and reepithelialization, promoting wound contraction and angiogenesis, and inhibiting bacterial virulence effects. In addition, β‐blockers shorten wound healing periods in patients with severe thermal damage by reducing the hypermetabolic response. While β‐blockers promote/inhibit corneal epithelial cell regeneration and restores limbal stem/progenitor cells function, it could well accelerate/delay corneal wound healing. Given these meaningful effects, a growing number of studies are focused on examining the efficacy and safety of β‐blockers in soft tissue wound repair, including acute and chronic wounds, severe thermal damage, ulcerated infantile hemangioma, corneal wounds, and other soft tissue disorders. However, an intensive investigation on their acting mechanisms is imperatively needed. The purpose of this article is to summerize the roles of β‐blockers in soft tissue wound healing and explore their clinical applications.

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Trace amines produced by skin bacteria accelerate wound healing in mice

Cited by 37 publications

References 67 publications

The Neuromodulator-Encoding sadA Gene Is Widely Distributed in the Human Skin Microbiome

The Neuromodulator-Encoding sadA Gene Is Widely Distributed in the Human Skin Microbiome

The Genome of Staphylococcus epidermidis O47

Mechanism and application of β‐adrenoceptor blockers in soft tissue wound healing

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