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Proceedings of the National Academy of... Mar 2022SignificanceWe report the development of peptidomimetic antibiotics derived from a natural antimicrobial peptide, human α-defensin 5. By engaging multiple bacterial...
SignificanceWe report the development of peptidomimetic antibiotics derived from a natural antimicrobial peptide, human α-defensin 5. By engaging multiple bacterial targets, the lead compound is efficacious in vitro and in vivo against bacteria with highly inducible antibiotic resistance, promising a useful therapeutic agent for the treatment of infections caused by antibiotic-resistant bacteria.
Topics: Anti-Bacterial Agents; Defensins; Drug Discovery; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Molecular Structure; Peptidomimetics; Structure-Activity Relationship
PubMed: 35238683
DOI: 10.1073/pnas.2117283119 -
Molecules (Basel, Switzerland) Aug 2018In this narrative review, we comprehensively review the available information about the recognition, structure, and dynamics of antimicrobial peptides (AMPs). Their... (Review)
Review
In this narrative review, we comprehensively review the available information about the recognition, structure, and dynamics of antimicrobial peptides (AMPs). Their complex behaviors occur across a wide range of time scales and have been challenging to portray. Recent advances in nuclear magnetic resonance and molecular dynamics simulations have revealed the importance of the molecular plasticity of AMPs and their abilities to recognize targets. We also highlight experimental data obtained using nuclear magnetic resonance methodologies, showing that conformational selection is a major mechanism of target interaction in AMP families.
Topics: Animals; Anti-Infective Agents; Defensins; Drug Discovery; Humans; Magnetic Resonance Spectroscopy; Molecular Dynamics Simulation; Peptides; Protein Conformation
PubMed: 30111717
DOI: 10.3390/molecules23082040 -
Poultry Science Feb 2023The yolk sac is a multifunctional organ, which not only participates in nutrient absorption, but also plays an important role in immune function. The objective of this...
The yolk sac is a multifunctional organ, which not only participates in nutrient absorption, but also plays an important role in immune function. The objective of this study was to compare the mRNA abundance of avian β-defensin 10 (AvBD10) and 3 cathelicidins (CATH1, CATH2, and CATH3) in the yolk sac tissue (YST) of commercial broilers and white egg and brown egg commercial layers. AvBD10 and CATH mRNA abundance was analyzed using two-way ANOVA and Tukey's test, with P < 0.05 being considered significant. AvBD10 and CATH mRNA showed similar temporal expression patterns in the YST of both broiler and layers, with an increase from embryonic day (E) 7 to E9 through E13 followed by a decrease to day of hatch. AvBD10 mRNA showed a breed × age interaction with greater expression in the YST of both layers compared to broilers at E9 and E11. CATH1 mRNA was greater in the YST of brown egg layers than broilers. CATH2 mRNA showed a breed × age interaction, with greater expression in the YST of brown egg layers than broilers at E11. CATH3 mRNA showed no difference in the YST between layers and broilers. Because broilers and brown egg layers are genetically related, these results show that selection for production parameters (broiler vs. layer) and not genetic relatedness (white egg layer vs. brown egg layer and broilers) is the basis for the differences in AvBD10, CATH1, and CATH2 mRNA in the YST of broilers and layers. The yolk-free body weights of broiler embryos were greater than that of both brown and white egg layers from E9 to 17. One possible explanation is that the reduced expression of AvBD10, CATH1 and CATH2 mRNA in the YST of broilers compared to layers at E9 and 11 may be due to faster embryonic growth at the expense of host defense peptide expression in broilers compared to layers.
Topics: Animals; Chickens; Yolk Sac; beta-Defensins; Cathelicidins; RNA, Messenger
PubMed: 36481712
DOI: 10.1016/j.psj.2022.102334 -
Innate Immunity Jun 2010Defensins were first identified in 1985 and are now recognized as part of a large family of antimicrobial peptides, divided into three categories: alpha-, beta-, and... (Review)
Review
Defensins were first identified in 1985 and are now recognized as part of a large family of antimicrobial peptides, divided into three categories: alpha-, beta-, and -defensins. These defensin classes differ in structure, sites of expression and biological activities. Human alpha-defensins include peptides that are expressed primarily in neutrophils, whereas human beta-defensins are widely expressed in epithelial cells, including those lining the respiratory tract. Defensins were first studied for their broad spectrum activity against bacteria, fungi and viruses; however, it is now clear that they also recruit inflammatory cells and promote innate and adaptive immune responses. Recent evidence shows that defensins have anti-inflammatory effects as well. Hence, defensins can participate in all phases of an immune response in the lung, including initial killing of pathogens and mounting - and resolution -- of an immune or inflammatory response. The cathelicidin, LL-37, is an antimicrobial peptide produced by neutrophils and respiratory epithelial cells that has similar roles in lung immunity as the defensins. A major challenge for the coming years will be to sort out the relative contributions of defensins and LL-37 to overall immune responses in the lung and to determine which of their many in vitro activities are most important for lung immunity.
Topics: Animals; Anti-Infective Agents; Cathelicidins; Defensins; Epithelial Cells; Humans; Immunity, Innate; Lung; Neutrophils
PubMed: 20418263
DOI: 10.1177/1753425910365734 -
Journal of Leukocyte Biology Jan 2010Defensins are widespread in nature and have activity against a broad range of pathogens. Defensins have direct antimicrobial effects and also modulate innate and... (Review)
Review
Defensins are widespread in nature and have activity against a broad range of pathogens. Defensins have direct antimicrobial effects and also modulate innate and adaptive immune responses. We consider the role of human defensins and the cathelicidin LL-37 in defense of respiratory, gastrointestinal, and genitourinary tracts and the oral cavity, skin, and eye. Human beta-defensins (hBDs) and human defensins 5 and 6 (HD5 and -6) are involved most obviously in mucosal responses, as they are produced principally by epithelial cells. Human alpha-defensins 1-4 (or HNPs 1-4) are produced principally by neutrophils recruited to the mucosa. Understanding the biology of defensins and LL-37 is the beginning to clarify the pathophysiology of mucosal inflammatory and infectious diseases (e.g., Crohn's disease, atopic dermatitis, lung or urinary infections). Challenges for these studies are the redundancy of innate defense mechanisms and the presence and interactions of many innate defense proteins in mucosal secretions.
Topics: Antimicrobial Cationic Peptides; Defensins; Eye; Gastric Mucosa; Humans; Immunity, Innate; Immunity, Mucosal; Infections; Intestinal Mucosa; Mouth Mucosa; Organ Specificity; Respiratory Mucosa; Skin; Urogenital System; Cathelicidins
PubMed: 19808939
DOI: 10.1189/jlb.0609382 -
Journal of Cosmetic Dermatology Feb 2023Defensins are peptides capable of reactivating latent LGR6 stem cells in the basal layer. When applied topically, these peptides can reduce signs of skin aging and...
BACKGROUND AND AIMS
Defensins are peptides capable of reactivating latent LGR6 stem cells in the basal layer. When applied topically, these peptides can reduce signs of skin aging and increase dermal thickness. This study investigates the effects of a topical defensin formulation on extremity skin composition.
METHODS
An open label, single arm clinical trial was conducted on participants with dry, photoaged, or dull skin. A defensin-containing hand and body cream was applied twice daily for 6 weeks to the hands, forearms, elbows, and knees. Photographs and objective measurements of skin hydration, viscoelasticity (VE), retraction time (RT), thickness, density/transepidermal water loss (TEWL), as well as self-evaluation of skin quality and characteristics were obtained pre- and post- intervention.
RESULTS
After the study period, RT decreased by 56% across all body sites (p < 0.001) and VE improved at the elbow (125%, p = 0.009) and knee (110%, p < 0.001). Skin density also increased in all 4 body sites (40%, p < 0.001), while skin thickness increased at the elbow (29%, p = 0.03) and knee (17%, p = 0.04). Skin hydration increased at the elbow, knee, and forearm by 99%, 28%, and 16%, respectively (p < 0.05), while TEWL improved at the elbow only (-39%, p = 0.02). Patients' self-evaluations showed improvements in overall skin quality and in the domains of dryness, ashiness, wrinkling, pigmentation, redness, roughness, and discomfort (p < 0.05).
CONCLUSIONS
Following 6-week use of a defensin-containing cream, subjects reported significant improvement across many subjective skin domains. Similarly, objective measurements demonstrated significant improvement in skin architecture at select sites.
Topics: Humans; Defensins; Emollients; Epidermis; Skin; Skin Aging; Skin Cream
PubMed: 35621235
DOI: 10.1111/jocd.15118 -
Immunity Sep 2022The full range of receptors through which antimicrobial peptides exert their immunologic effects remains incompletely explored. Dong and colleagues identify Mgrpra2 as a...
The full range of receptors through which antimicrobial peptides exert their immunologic effects remains incompletely explored. Dong and colleagues identify Mgrpra2 as a G-coupled protein receptor on neutrophils, for which keratinocyte-derived Beta-defensins serve as key ligands. Binding of Mgrpra2 leads to release of neutrophil granules and Il-1β, which helps shape skin microbiome composition and augments cutaneous defense against bacterial infection.
Topics: Carrier Proteins; Keratinocytes; Neutrophils; Skin; beta-Defensins
PubMed: 36103856
DOI: 10.1016/j.immuni.2022.08.014 -
Proceedings of the Japan Academy.... 2012Defensins comprise a family of cationic antimicrobial peptides containing a specific six-cysteine motif. Their contribution to the host defense against microbial... (Review)
Review
Antimicrobial peptide defensin: identification of novel isoforms and the characterization of their physiological roles and their significance in the pathogenesis of diseases.
Defensins comprise a family of cationic antimicrobial peptides containing a specific six-cysteine motif. Their contribution to the host defense against microbial invasion and the control of normal flora have been previously described. Some of the β-defensin isoforms are predominantly expressed in the epididymis and showed a region-specific expression pattern in the epididymis, which thus suggested that these isoforms may possess epididymis-specific functions in addition to antimicrobial activities. A sequence variant of the β-defensin 126 gene has been shown to be associated with reductions in the human sperm function, thus supporting this hypothesis. Furthermore, defensins have the capacity to chemoattract immune cells and induce the secretion of inflammatory cytokines. Mice expressing human neutrophil α-defensin showed more severe lung injuries after the aspiration of acidic contents than did control mice. Recent investigations regarding copy number variations of human defensin genes also suggest the significance of defensin in the pathogenesis or the worsening of chronic obstructive pulmonary diseases, sepsis and psoriasis.
Topics: Amino Acid Sequence; Animals; Defensins; Disease; Genomics; Humans; Immunity; Molecular Sequence Data; Protein Isoforms
PubMed: 22498979
DOI: 10.2183/pjab.88.152 -
Microbial Pathogenesis Jun 2021Antimicrobial peptides (AMPs) are ubiquitously present small peptides, which play a critical function in the innate immune system. The defensin class of AMPs represented... (Review)
Review
Antimicrobial peptides (AMPs) are ubiquitously present small peptides, which play a critical function in the innate immune system. The defensin class of AMPs represented an evolutionarily ancient family containing cationic cysteine residue and frequently expressed in epithelial or neutrophils cells. It plays myriad functions in host innate immune responses against various infection. Defensin has a broad spectrum of antimicrobial activities, including anti-bacteria, anti-viruses (AVPs), anti-fungi, anti-cancers, and also overcoming bacterial drug resistance. In this review, we compiled the progress on defensin, particularly incorporating the mechanism of action, their application as an antiviral agent, prospects in different areas, and limitations to be solved as an antiviral peptide. Defensins were explored, in particular, their capacity to stimulate innate and adaptive immunity by trigging as anti-coronavirus (COVID-19) peptides. The present review summarised its immunomodulatory and immunoenhancing properties and predominantly focused on its promising therapeutic adjuvant choices for combat against viral infection.
Topics: COVID-19; Defensins; Humans; Immunity, Innate; Peptides; SARS-CoV-2; Virus Diseases
PubMed: 33933603
DOI: 10.1016/j.micpath.2021.104930 -
EMBO Molecular Medicine Feb 2022The development of eukaryote-derived antimicrobial peptides as systemically administered drugs has proven a challenging task. Here, we report the first human oral...
The development of eukaryote-derived antimicrobial peptides as systemically administered drugs has proven a challenging task. Here, we report the first human oral actinomyces-sourced defensin-actinomycesin-that shows promise for systemic therapy. Actinomycesin and its homologs are only present in actinobacteria and myxobacteria, and share similarity with a group of ancient invertebrate-type defensins reported in fungi and invertebrates. Signatures of natural selection were detected in defensins from the actinomyces colonized in human oral cavity and ruminant rumen and dental plaque, highlighting their role in adaptation to complex multispecies bacterial communities. Consistently, actinomycesin exhibited potent antibacterial activity against oral bacteria and clinical isolates of Staphylococcus and synergized with two classes of human salivary antibacterial factors. Actinomycesin specifically inhibited bacterial peptidoglycan synthesis and displayed weak immunomodulatory activity and low toxicity on human and mammalian cells and ion channels in the heart and central nervous system. Actinomycesin was highly efficient in mice infected with Streptococcus pneumoniae and mice with MRSA-induced experimental peritoneal infection. This work identifies human oral bacteria as a new source of systemic anti-infective drugs.
Topics: Actinomyces; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Defensins; Humans; Mice
PubMed: 34927385
DOI: 10.15252/emmm.202114499