Functional and structural characterization of recombinant dermcidin-1L, a human antimicrobial peptide

Lai, Yuping; Peng, Yifei; Zuo, Yi Y.; Li, Jun; Huang, Jing; Wang, Lin‐Fa; Wu, Zirong

doi:10.1016/j.bbrc.2004.12.143

Cited by 60 publications

(51 citation statements)

References 23 publications

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“…1A). In eccrine sweat, differently processed DCD-derived C-terminal peptides comprising 48 aa residues (DCD-1L), 47 aa residues (DCD-1), and shorter fragments were detected (Flad et al 2002), and additional studies confirmed the antimicrobial activity of DCD-1L and DCD-1 against a variety of pathogenic micro-organisms (Schittek et al 2001, Vuong et al 2004, Lai et al 2005. Human sweat contains 1-10 mg/ml DCD-1, which is a concentration that is toxic to most micro-organisms that have been tested (Flad et al 2002).…”

Section: Introductionmentioning

confidence: 90%

Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice

Kim¹,

Ka²,

Moon³

et al. 2008

Journal of Endocrinology

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Dermcidin (DCD), an antimicrobial peptide that is secreted by sweat glands, is reportedly a human homolog of mouse proteolysis-inducing factor. This study was conducted to investigate the effect of DCD on body fat mobilization. The expression level of DCD in the livers of Ad-DCD-injected mice was higher than in those of Ad-b-galactosidase (Ad-bgal)-injected mice 7 days after injection. In addition, injection with the Ad-DCD virus led to decreased body weight and epididymal fat mass when compared with controls. The plasma triglyceride level was decreased, whereas the free fatty acid and glycerol levels were increased in the Ad-DCDinjected group. Epididymal adipose tissues obtained from Ad-DCD-injected mice consisted of smaller adipocytes than tissues obtained from Ad-b-gal-injected mice. The gene expression profiles revealed an upregulation of hormonesensitive lipase and adipose fatty acid-binding protein, both of which are involved in adipocyte lipolysis, in Ad-DCDinjected mice, and this lipolytic effect of DCD paralleled the increase of circulating tumor necrosis factor-a (TNF-a) level that was observed. The perilipin levels in adipose tissue were decreased in Ad-DCD-injected mice when compared with those of the control mice. Taken together, these results suggest that DCD-mediated body fat reduction might occur as a result of TNF-a-induced downregulation of perilipin in adipose tissue.

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Section: Introductionmentioning

confidence: 90%

Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice

Kim¹,

Ka²,

Moon³

et al. 2008

Journal of Endocrinology

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“…In eccrine sweat, different processed DCD-derived C-terminal peptides of 48-aa residues (DCD-1L), 47-aa residues (DCD-1), and shorter fragments can be detected by surface-enhanced laser desorption ionization timeof-flight mass spectrometry (SELDI-TOF-MS) (13). DCD-1L and DCD-1 show antimicrobial activity against pathogenic microorganisms such as Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Enterococcus faecalis, and Candida albicans under in vitro conditions resembling human sweat (5,14,15). In human sweat, 1-10 g/ml DCD-1 is found, a concentration that is toxic to most microorganisms tested (13).…”

mentioning

confidence: 99%

Deficiency of Dermcidin-Derived Antimicrobial Peptides in Sweat of Patients with Atopic Dermatitis Correlates with an Impaired Innate Defense of Human Skin In Vivo

Rieg

Steffen²,

Seeber³

et al. 2005

The Journal of Immunology

253

185

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Antimicrobial peptides are an integral part of the epithelial innate defense system. Dermcidin (DCD) is a recently discovered antimicrobial peptide with a broad spectrum of activity. It is constitutively expressed in human eccrine sweat glands and secreted into sweat. Patients with atopic dermatitis (AD) have recurrent bacterial or viral skin infections and pronounced colonization with Staphylococcus aureus. We hypothesized that patients with AD have a reduced amount of DCD peptides in sweat contributing to the compromised constitutive innate skin defense. Therefore, we performed semiquantitative and quantitative analyses of DCD peptides in sweat of AD patients and healthy subjects using surface-enhanced laser desorption ionization time-of-flight mass spectrometry and ELISA. The data indicate that the amount of several DCD-derived peptides in sweat of patients with AD is significantly reduced. Furthermore, compared with atopic patients without previous infectious complications, AD patients with a history of bacterial and viral skin infections were found to have significantly less DCD-1 and DCD-1L in their sweat. To analyze whether the reduced amount of DCD in sweat of AD patients correlates with a decreased innate defense, we determined the antimicrobial activity of sweat in vivo. We showed that in healthy subjects, sweating leads to a reduction of viable bacteria on the skin surface, but this does not occur in patients with AD. These data indicate that reduced expression of DCD in sweat of patients with AD may contribute to the high susceptibility of these patients to skin infections and altered skin colonization.

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“…DCD-1 is comprised of 47 amino acids and shows antimicrobial activity against a variety of pathogenic microorganisms (15,17,18). It was recently reported that although the antimicrobial activity of DCD-1 originates with its binding to bacterial membranes, the bacterial membrane not very permeable to DCD-1 (18).…”

Section: Membrane Interaction Of Dcd and Its Fragmentsmentioning

confidence: 99%

“…It is produced through proteolytic processing of a 110-amino acid precursor protein that has no homology to other known antimicrobial peptides (15, 16). The processed peptide, DCD-1, has 47 amino acids and shows a broad spectrum of antimicrobial activity against a variety of pathogenic microorganisms (15,17,18). Using immune-EM, it was recently shown that the antimicrobial activity of DCD-1 originates with its binding to the bacterial membrane, and that it effectively kills Staphylococcus epidermidis (18).…”

Section: Introductionmentioning

confidence: 99%

“…DCD-1L, which is produced by adding a leucine residue to the C-terminus of DCD-1, shows stronger antimicrobial activity than the parent peptide (15). It is especially noteworthy that DCD-1L exhibits activity against drug-resistant S. aureus, as well as other Gram-positive and Gram-negative bacterial strains (17). In the present study, we used nuclear magnetic resonance (NMR) spectroscopy to determine, for the first time, the solution structure of DCD-1L in a bacterial membrane-mimetic environment.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of the solution structure of the human antibiotic peptide dermcidin and its interaction with phospholipid vesicles

Jung

Yang²,

Sim³

et al. 2010

BMB Reports

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Dermcidin is a human antibiotic peptide that is secreted by the sweat glands and has no homology to other known antimicrobial peptides. As an initial step toward understanding dermcidin's mode of action at bacterial membranes, we used homonuclear and heteronuclear NMR to determine the conformation of the peptide in 50% trifluoroethanol solution. We found that dermcidin adopts a flexible amphipathic α-helical structure with a helix-hinge-helix motif, which is a common molecular fold among antimicrobial peptides. Spin-down assays of dermcidin and several related peptides revealed that the affinity with which dermcidin binds to bacterial-mimetic membranes is primarily dependent on its amphipathic α-helical structure and its length (＞30 residues); its negative net charge and acidic pI have little effect on binding. These findings suggest that the mode of action of dermcidin is similar to that of other membrane-targeting antimicrobial peptides, though the details of its antimicrobial action remain to be determined [BMB reports 2010; 43(5): 362-368] INTRODUCTIONAntimicrobial peptides are produced in a wide range of animals for innate host defense and show a broad spectrum of antimicrobial activity (1-4). Despite the remarkable diversity of their amino acid compositions, antimicrobial peptides show several common features, including the presence of multiple basic amino acids and amphipathic structures with clusters of hydrophobic and hydrophilic amino acids (5-8). Recent studies of the modes of action of various antimicrobial peptides have revealed that their cationic nature contributes to their initial binding to negatively charged bacterial membranes through electrostatic interaction, while their amphipathic structures enhance peptide-lipid interactions at the water-bilayer interface, ultimately leading to cell death via pore formation or membrane disintergration (9-14).Dermcidin (DCD) is an antimicrobial peptide found in human sweat. It is produced through proteolytic processing of a 110-amino acid precursor protein that has no homology to other known antimicrobial peptides (15, 16). The processed peptide, DCD-1, has 47 amino acids and shows a broad spectrum of antimicrobial activity against a variety of pathogenic microorganisms (15,17,18). Using immune-EM, it was recently shown that the antimicrobial activity of DCD-1 originates with its binding to the bacterial membrane, and that it effectively kills Staphylococcus epidermidis (18).DCD-1L, which is produced by adding a leucine residue to the C-terminus of DCD-1, shows stronger antimicrobial activity than the parent peptide (15). It is especially noteworthy that DCD-1L exhibits activity against drug-resistant S. aureus, as well as other Gram-positive and Gram-negative bacterial strains (17). In the present study, we used nuclear magnetic resonance (NMR) spectroscopy to determine, for the first time, the solution structure of DCD-1L in a bacterial membrane-mimetic environment. In addition, to investigate the interaction between DCD-1L and bacterial membranes, we sy...

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Functional and structural characterization of recombinant dermcidin-1L, a human antimicrobial peptide

Cited by 60 publications

References 23 publications

Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice

Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice

Deficiency of Dermcidin-Derived Antimicrobial Peptides in Sweat of Patients with Atopic Dermatitis Correlates with an Impaired Innate Defense of Human Skin In Vivo

Analysis of the solution structure of the human antibiotic peptide dermcidin and its interaction with phospholipid vesicles

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