Defensins

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Beta defensins are a family of vertebrate defensins. The beta defensins are antimicrobial peptides implicated in the resistance of epithelial surfaces to microbial colonization. Defensins are kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, [1] containing three pairs of intramolecular disulfide bonds. On the basis of their size and pattern of disulfide bonding, mammalian defensins are classified into alpha , beta and theta categories. Every mammalian species explored thus far has beta-defensins. In cows, as many as 13 beta-defensins exist in neutrophils.

Defensins

Defensins are small cysteine -rich cationic proteins across cellular life, including vertebrate [1] and invertebrate [2] animals, plants , [3] [4] and fungi. They are variously active against bacteria , fungi and many enveloped and nonenveloped viruses. They are typically amino acids in length, with three or four highly conserved disulphide bonds. In animals, they are produced by cells of the innate immune system and epithelial cells , whereas in plants and fungi they are produced by a wide variety of tissues. An organism usually produces many different defensins, some of which are stored inside the cells e. For those that directly kill microbes, their mechanism of action varies from disruption of the microbial cell membrane to metabolic disruption. The name 'defensin' was coined in the mids, though the proteins have been called 'Cationic Antimicrobial Proteins,' 'Neutrophil peptides,' 'Gamma thionins' amongst others. Proteins called 'defensins' are not all evolutionarily related to one another. In all families, the underlying genes responsible for defensin production are highly polymorphic. The disulfide linkages formed by the cysteines have been suggested to be essential for activities related to innate immunity in mammals, but are not necessarily required for antimicrobial activity.

Innate defensins peptide protects the skin from invasive bacterial infection. Human small intestine, immunostained for HD

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. As a family of cationic host defense peptides, defensins are mainly synthesized by Paneth cells, neutrophils, and epithelial cells, contributing to host defense. Their biological functions in innate immunity, as well as their structure and activity relationships, along with their mechanisms of action and therapeutic potential, have been of great interest in recent years.

Defensins represent an evolutionary ancient family of antimicrobial peptides that play diverse roles in human health and disease. Defensins are cationic cysteine-containing multifunctional peptides predominantly expressed by epithelial cells or neutrophils. Defensins play a key role in host innate immune responses to infection and, in addition to their classically described role as antimicrobial peptides, have also been implicated in immune modulation, fertility, development, and wound healing. Aberrant expression of defensins is important in a number of inflammatory diseases as well as modulating host immune responses to bacteria, unicellular pathogens, and viruses. In parallel with their role in immunity, in other species, defensins have evolved alternative functions, including the control of coat color in dogs. Defensin genes reside in complex genomic regions that are prone to structural variations and some defensin family members exhibit copy number variation CNV. Structural variations have mediated, and continue to influence, the diversification and expression of defensin family members. It evaluates current evidence linking defensin CNV to autoimmune disease i. The defensins represent a class of cationic antimicrobial peptides that play pivotal roles in innate and adaptive immunity as well as roles in non-immunological processes.

Defensins

Enteric alpha-defensins are potent effectors of innate immunity that are abundantly expressed in the small intestine. Certain enteric bacteria and viruses are resistant to defensins and even appropriate them to enhance infection despite neutralization of closely related microbes. We therefore hypothesized that defensins impose selective pressure during fecal-oral transmission. Upon passaging a defensin-sensitive serotype of adenovirus in the presence of a human defensin, mutations in the major capsid protein hexon accumulated. In contrast, prior studies identified the vertex proteins as important determinants of defensin antiviral activity. Infection and biochemical assays suggest that a balance between increased cell binding and a downstream block in intracellular trafficking mediated by defensin interactions with all of the major capsid proteins dictates the outcome of infection. These results extensively revise our understanding of the interplay between defensins and non-enveloped viruses. Furthermore, they provide a feasible rationale for defensins shaping viral evolution, resulting in differences in infection phenotypes of closely related viruses. Defensins are potent antimicrobial peptides that are found on human mucosal surfaces and can directly neutralize viruses.

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Despite these benefits, no clinical trials currently utilize human defensin molecules in infectious disease treatment. Human beta-defensin-2 in oral cancer with opportunistic candida infection. Furthermore, plant-derived Chinese herbal medicines dehydroandrographolide DA and reishi are also effective regulators of defensin expression. Antimicrobial mechanisms of defensin. Defensin and lactoferrin levels are found to be elevated in the cerebrospinal fluid of children with meningitis [ 8 ]. Miani et al. Search ADS. Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds; pp. Mechanism of bactericidal activity. Molecular Biology and Evolution. Myeloperoxidase Defensins neutral serine proteases Proteinase 3 Lysozyme Bactericidal permeability-increasing protein Collagenase. We will highlight the current knowledge base regarding mammalian defensins and their roles in regulating host health, thus providing a theoretical basis for clinical therapeutic strategies targeting defensins to treat disease. Wiles K. Purification and antimicrobial properties of three defensins from rat neutrophils. Trajectories of kidney function in diabetes: a clinicopathological update.

Naturally occurring antimicrobial cationic polypeptides play a major role in innate and adaptive immunity. These polypeptides are found to be either linear and unstructured or structured through disulfide bonds. Among the structured antimicrobial polypeptides, defensins comprise a family of cysteine-rich cationic polypeptides that contribute significantly to host defense against the invasion of microorganisms in animals, humans, insects and plants.

An important paper that showed the serial permeabilization of outer and inner membranes of Escherichia. The expression of antimicrobial peptides is significantly altered in cutaneous squamous cell carcinoma and precursor lesions. However, a recent study of cationic antimicrobial peptides of varying structures with a planar bilayer and with the cytoplasmic membrane of E. High concentrations of sPLA are also present in human tears. The human cationic antimicrobial protein hCAP is expressed in the epithelium of human epididymis, is present in seminal plasma at high concentrations, and is attached to spermatozoa. USA 99 , — Lactoferrin binds bacterial lipopolysaccharide with high affinity and also binds various other proteins. Salivary antimicrobial peptides in early detection of periodontitis. The effect of defensins on protozoans has received little study, at least in vertebrates. Key determinants of human alpha-defensin 5 and 6 for enhancement of HIV infectivity. A deeper understanding of the interactions between probiotics and defensins is necessary. Ganz T. There are many more members of the defensin gene family than has previously been suspected. Schonwetter, B.