Expression of the sweat-derived innate defence antimicrobial peptide dermcidin is not impaired in<i>Staphylococcus aureus</i>colonization or recurrent skin infections

Rieg, Siegbert; Saborowski, Viola; Kern, Winfried V.; Jonas, Daniel E; Bruckner‐Tuderman, Leena; Hofmann, Silke

doi:10.1111/ced.12189

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…Bacterial and viral infections are a major threat to human health; these invading pathogens have evolved resistance to available small-molecule antimicrobial therapeutics (Davies and Davies, 2010). Skin is the organ most exposed between the body and microorganisms, including common antibiotic resistant bacteria such as Staphylococcus aureus (Rieg et al, 2014). Schittek et al (2001) found that dermcidin has antimicrobial activity against Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and Candida albicans, which limits skin infection of potential pathogens a few hours after bacterial colonization, but that lactoferrin in sweat does not show an effective role in the defense against bacteria.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Sweat Exosome Suggests its Involvement in Skin Immunity

Liu

2018

Journal of Investigative Dermatology

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Healthy human skin sustains an effective immune defense mechanism, formed by a complex physical and chemical epidermal barrier that coordinates with different cellular components of the skin immune system. However, the mechanism by which skin cells regulate local immune homeostasis in health and disease contexts is not well known. To investigate whether exosomes exist in sweat, sweat samples from healthy individuals were collected after aerobic exercise. Sweat exosome was isolated via differential ultracentrifugation, observed under transmission electron microscopy, measured by dynamic light scattering, and confirmed by immunoblot. Further, shotgun liquid chromatography (LC)-mass spectrometry (MS)/MS analysis was conducted to investigate the proteomic profiling of sweat exosome. Secreted exosome was detected in human sweat. A total of 1,062 proteins were identified in sweat exosome, including 997 different proteins compared with sweat proteomics and 896 unique proteins compared with urine, saliva, and plasma exosomes. Diverse antimicrobial peptides and immunological factors were found in sweat exosome, suggesting the involvement of exosome in skin immunity. This study provides direct evidence that secreted exosomes exist in human sweat. The proteomic profiling of sweat exosome provides insight into sweat features and the potential physiological significance of exosomes in immune homeostasis.

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Section: Discussionmentioning

confidence: 99%

Proteomic Profiling of Sweat Exosome Suggests its Involvement in Skin Immunity

Liu

2018

Journal of Investigative Dermatology

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“…Furthermore, dermcidin variants as well as fragments were also detected. It appears that the level of dermcidin did not vary between healthy people and infected patients [ 91 ]. In addition, dermcidin may be related to other human diseases such as cancer and atherosclerosis [ 92 , 93 ].…”

Section: Identification Of Human Antimicrobial Peptidesmentioning

confidence: 99%

Human Antimicrobial Peptides and Proteins

2014

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As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc) are able to induce the expression of antimicrobial peptides, opening new avenues to the development of anti-infectious drugs.

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“…This lack of antimicrobial defense correlated with an impaired ability of sweat to eradicate bacteria on the skin of these patients (Rieg et al, 2005;Schittek, 2011). In contrast, Rieg and colleagues recently reported in a correlation study that patients with recurrent S. aureus skin and soft tissue infections and healthy people have a comparable level of dermcidin-derived peptides in their sweat (Rieg et al, 2014). The high abundance of dermcidin in the secretome of healthy individuals, which is known to be exclusively expressed by eccrine sweat glands in the skin (Rieg et al, 2004;Schittek, 2012), suggests that a majority of the identified proteins in the skin secretome of healthy individuals are derived from eccrine sweat.…”

Section: Prolactin-inducible Protein (P12273)mentioning

confidence: 98%

Quantitative Proteomics of the Human Skin Secretome Reveal a Reduction in Immune Defense Mediators in Ectodermal Dysplasia Patients

Burian

Velić

Matic

et al. 2015

Journal of Investigative Dermatology

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In healthy human skin host defense molecules such as antimicrobial peptides (AMPs) contribute to skin immune homeostasis. In patients with the congenital disease ectodermal dysplasia (ED) skin integrity is disturbed and as a result patients have recurrent skin infections. The disease is characterized by developmental abnormalities of ectodermal derivatives and absent or reduced sweating. We hypothesized that ED patients have a reduced skin immune defense because of the reduced ability to sweat. Therefore, we performed a label-free quantitative proteome analysis of wash solution of human skin from ED patients or healthy individuals. A clear-cut difference between both cohorts could be observed in cellular processes related to immunity and host defense. In line with the extensive underrepresentation of proteins of the immune system, dermcidin, a sweat-derived AMP, was reduced in its abundance in the skin secretome of ED patients. In contrast, proteins involved in metabolic/catabolic and biosynthetic processes were enriched in the skin secretome of ED patients. In summary, our proteome profiling provides insights into the actual situation of healthy versus diseased skin. The systematic reduction in immune system and defense-related proteins may contribute to the high susceptibility of ED patients to skin infections and altered skin colonization.

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Expression of the sweat-derived innate defence antimicrobial peptide dermcidin is not impaired inStaphylococcus aureuscolonization or recurrent skin infections

Cited by 6 publications

References 9 publications

Proteomic Profiling of Sweat Exosome Suggests its Involvement in Skin Immunity

Proteomic Profiling of Sweat Exosome Suggests its Involvement in Skin Immunity

Human Antimicrobial Peptides and Proteins

Quantitative Proteomics of the Human Skin Secretome Reveal a Reduction in Immune Defense Mediators in Ectodermal Dysplasia Patients

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