Showing papers on "Antimicrobial peptides published in 2011"
TL;DR: Several intact proteins or protein fragments are now being shown to have inherent antimicrobial activity, suggesting a better understanding of the structure-activity relationships of AMPs is required to facilitate the rational design of novel antimicrobial agents.
1,249 citations
TL;DR: An important role is shown for neutrophils in lupus pathogenesis, whereby neutrophil activated by anti-self antibodies release NETs, which contain antimicrobial peptides complexed with self-DNA and can entrap bacteria, enabling them to be killed.
Abstract: Systemic lupus erythematosus (SLE) is a severe and incurable autoimmune disease characterized by chronic activation of plasmacytoid dendritic cells (pDCs) and production of autoantibodies against nuclear self-antigens by hyperreactive B cells. Neutrophils are also implicated in disease pathogenesis; however, the mechanisms involved are unknown. Here, we identified in the sera of SLE patients immunogenic complexes composed of neutrophil-derived antimicrobial peptides and self-DNA. These complexes were produced by activated neutrophils in the form of web-like structures known as neutrophil extracellular traps (NETs) and efficiently triggered innate pDC activation via Toll-like receptor 9 (TLR9). SLE patients were found to develop autoantibodies to both the self-DNA and antimicrobial peptides in NETs, indicating that these complexes could also serve as autoantigens to trigger B cell activation. Circulating neutrophils from SLE patients released more NETs than those from healthy donors; this was further stimulated by the antimicrobial autoantibodies, suggesting a mechanism for the chronic release of immunogenic complexes in SLE. Our data establish a link between neutrophils, pDC activation, and autoimmunity in SLE, providing new potential targets for the treatment of this devastating disease.
1,104 citations
TL;DR: An overview of the intestinal microbiota is provided and the cell biology of Paneth cells is described, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis.
Abstract: Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.
944 citations
TL;DR: An overview of the antimicrobial and immunomodulatory activities of cationic HDPs is provided, and their potential application as beneficial therapeutics in overcoming infectious diseases is discussed.
Abstract: With the rapid rise in the emergence of bacterial strains resistant to multiple classes of antimicrobial agents, there is an urgent need to develop novel antimicrobial therapies to combat these pathogens. Cationic host defence peptides (HDPs) and synthetic derivatives termed innate defence regulators (IDRs) represent a promising alternative approach in the treatment of microbial-related diseases. Cationic HDPs (also termed antimicrobial peptides) have emerged from their origins as nature’s antibiotics and are widely distributed in organisms from insects to plants to mammals and non-mammalian vertebrates. Although their original and primary function was proposed to be direct antimicrobial activity against bacteria, fungi, parasites and/or viruses, cationic HDPs are becoming increasingly recognized as multifunctional mediators, with both antimicrobial activity and diverse immunomodulatory properties. Here we provide an overview of the antimicrobial and immunomodulatory activities of cationic HDPs, and discuss their potential application as beneficial therapeutics in overcoming infectious diseases.
541 citations
TL;DR: The present review provides a general overview of Bacillus bacteriocins, including primary structure, biochemical and genetic characterization, classification and potential applications in food preservation as natural preservatives and in human and animal health as alternatives to conventional antibiotics.
Abstract: Members of the genus Bacillus are known to produce a wide arsenal of antimicrobial substances, including peptide and lipopeptide antibiotics, and bacteriocins. Many of the Bacillus bacteriocins belong to the lantibiotics, a category of post-translationally modified peptides widely disseminated among different bacterial clades. Lantibiotics are among the best-characterized antimicrobial peptides at the levels of peptide structure, genetic determinants and biosynthesis mechanisms. Members of the genus Bacillus also produce many other nonmodified bacteriocins, some of which resemble the pediocin-like bacteriocins of the lactic acid bacteria (LAB), while others show completely novel peptide sequences. Bacillus bacteriocins are increasingly becoming more important due to their sometimes broader spectra of inhibition (as compared with most LAB bacteriocins), which may include Gram-negative bacteria, yeasts or fungi, in addition to Gram-positive species, some of which are known to be pathogenic to humans and/or animals. The present review provides a general overview of Bacillus bacteriocins, including primary structure, biochemical and genetic characterization, classification and potential applications in food preservation as natural preservatives and in human and animal health as alternatives to conventional antibiotics. Furthermore, it addresses their environmental applications, such as bioprotection against the pre- and post-harvest decay of vegetables, or as plant growth promoters.
508 citations
TL;DR: The overall results suggest that immobilized AMPs may be effective in the prevention of biofilm formation by reduction of microorganism survival post-contact with the coated biomaterial.
507 citations
TL;DR: The authors found that cells from the adaptive immune system—T cells—governed bacterial control by releasing the cytokine interferon-γ (IFN-γ), which then activated infected macrophages, inciting the cells to attack the invading M. tuberculosis.
Abstract: Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D–dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D–sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D–deficient serum with 25-hydroxyvitamin D3 restored IFN-γ–induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection.
464 citations
TL;DR: Data reveal a role for OMVs in contributing to innate bacterial defense by adsorption of antimicrobial peptides and bacteriophage, and conclude that OMV production may be an important factor in neutralizing environmental agents that target the outer membrane of Gram-negative bacteria.
Abstract: Outer membrane vesicles (OMVs) are constitutively produced by Gram-negative bacteria throughout growth and have proposed roles in virulence, inflammation, and the response to envelope stress. Here we investigate outer membrane vesiculation as a bacterial mechanism for immediate short-term protection against outer membrane acting stressors. Antimicrobial peptides as well as bacteriophage were used to examine the effectiveness of OMV protection. We found that a hyper-vesiculating mutant of Escherichia coli survived treatment by antimicrobial peptides (AMPs) polymyxin B and colistin better than the wild-type. Supplementation of E. coli cultures with purified outer membrane vesicles provided substantial protection against AMPs, and AMPs significantly induced vesiculation. Vesicle-mediated protection and induction of vesiculation were also observed for a human pathogen, enterotoxigenic E. coli (ETEC), challenged with polymyxin B. When ETEC with was incubated with low concentrations of vesicles concomitant with polymyxin B treatment, bacterial survival increased immediately, and the culture gained resistance to polymyxin B. By contrast, high levels of vesicles also provided immediate protection but prevented acquisition of resistance. Co-incubation of T4 bacteriophage and OMVs showed fast, irreversible binding. The efficiency of T4 infection was significantly reduced by the formation of complexes with the OMVs. These data reveal a role for OMVs in contributing to innate bacterial defense by adsorption of antimicrobial peptides and bacteriophage. Given the increase in vesiculation in response to the antimicrobial peptides, and loss in efficiency of infection with the T4-OMV complex, we conclude that OMV production may be an important factor in neutralizing environmental agents that target the outer membrane of Gram-negative bacteria.
452 citations
TL;DR: The state of the field is discussed and some questions that, if answered, could speed the discovery of clinically useful peptide antibiotics are posed.
Abstract: Multidrug antibiotic resistance is an increasingly serious public health problem worldwide. Thus, there is a significant and urgent need for the development of new classes of antibiotics that do not induce resistance. To develop such antimicrobial compounds, we must look toward agents with novel mechanisms of action. Membrane-permeabilizing antimicrobial peptides (AMPs) are good candidates because they act without high specificity toward a protein target, which reduces the likelihood of induced resistance. Understanding the mechanism of membrane permeabilization is crucial for the development of AMPs into useful antimicrobial agents. Various models, some phenomenological and others more quantitative or semimolecular, have been proposed to explain the action of AMPs. While these models explain many aspects of AMP action, none of the models captures all of the experimental observations, and significant questions remain unanswered. Here, we discuss the state of the field and pose some questions that, if answered, could speed the discovery of clinically useful peptide antibiotics.
433 citations
TL;DR: Examination of a complete mouse 65-kilodalton guanylate-binding protein (Gbp) gene family as part of a 43-member IFN-γ–inducible guanosine triphosphatase (GTPase) superfamily in mouse and human genomes found that at least four Gbpsferred cell-autonomous immunity to listerial or mycobacterial infection within macrophages and gene-deficient animals.
Abstract: Immune interferon gamma (IFN-γ) is essential for mammalian host defense against intracellular pathogens. IFN-γ induces nearly 2000 host genes, yet few have any assigned function. Here, we examined a complete mouse 65-kilodalton (kD) guanylate-binding protein (Gbp) gene family as part of a 43-member IFN-γ-inducible guanosine triphosphatase (GTPase) superfamily in mouse and human genomes. Family-wide loss-of-function analysis found that at least four Gbps--Gbp1, Gbp6, Gbp7, and Gbp10--conferred cell-autonomous immunity to listerial or mycobacterial infection within macrophages and gene-deficient animals. These Gbps solicited host defense proteins, including the phagocyte oxidase, antimicrobial peptides, and autophagy effectors, to kill intracellular bacteria. Thus, specific 65-kD Gbps coordinate a potent oxidative and vesicular trafficking program to protect the host from infection.
412 citations
TL;DR: The Barras and Méresse labs use a GFP fusion to an OxyR regulated gene to show that phagocyte‐derived H2O2 is gaining access to the Salmonella cytoplasm, suggesting that ROS are not diminished in this modified phagosome.
Abstract: Macrophages engulf and kill bacteria. Although the overall role of macrophages has been known for over 100 years, we understand surprisingly little of the actual mechanisms by which bacteria are destroyed. The cell biology of phagolysosomal formation is fairly well understood. Macrophages recognize and engulf bacteria into phagosomes, which subsequently acidify. These phagosomes mature into phagolysosomes upon vesicle-mediated delivery of various antimicrobial effectors, which include proteases, antimicrobial peptides, and lysozyme (Garin et al., 2001)(Figure 1). The phagolysosome is also a nutrient-limiting environment. Reactive oxygen species and reactive nitrogen species are produced in this compartment. The multi-subunit NADPH-dependent phagocytic oxidase (Phox or NOX2) is assembled on the phagolysosome membrane and pumps electrons into the compartment to reduce oxygen to superoxide anion (O2−). The inducible nitric oxide synthase uses arginine and oxygen as substrates to produce nitric oxide (Fang, 2004).
Figure 1
Reactive oxygen species in the Salmonella containing vacuole
Most bacteria are rapidly killed and degraded in the phagolysosome, making it difficult to dissect the mechanism of death. But a few bacteria have evolved to survive in macrophages. Salmonella use a type III secretion system to affect vesicular trafficking and maturation of the phagolysosome (Holden, 2002). It is presumed that the bacteria within this modified “Salmonella containing vacuole” (SCV) are subjected to a less intense antimicrobial response. However, the phagocytic arsenal still has a role in Salmonella pathogenesis and the bacteria must also be resistant to these antimicrobial factors. This balance between survival and killing makes Salmonella a powerful model to understand the mechanisms of action of the phagocytic effectors.
Reactive oxygen species (ROS) are critical weapons in the phagocyte arsenal. In theory, O2− and nitric oxide can combine to form highly reactive peroxynitrite (ONOO−). But the roles of Phox and iNOS are both temporally (Vazquez-Torres et al., 2000a) and genetically (Craig and Slauch, 2009) separable during Salmonella infection, suggesting that ONOO− is irrelevant when combating this pathogen. Studies by Aussel et al. (2011), reported in this volume, provide important information regarding Salmonella resistance to the ROS produced by Phox, and suggest that Salmonella relies less on blocking ROS formation than on scavenging.
TL;DR: It is found that this specially structured robust coating was extremely effective in resisting biofilm formation, and that the biofilm resistance depended on the nature of conjugated peptides.
TL;DR: This work reports that the weevil coleoptericin-A (ColA) antimicrobial peptide selectively targets endosymbionts within the bacteriocytes and regulates their growth through the inhibition of cell division, suggesting that long-term host-symbiont coevolution might have shaped immune effectors for symbiont maintenance.
Abstract: Vertically transmitted endosymbionts persist for millions of years in invertebrates and play an important role in animal evolution. However, the functional basis underlying the maintenance of these long-term resident bacteria is unknown. We report that the weevil coleoptericin-A (ColA) antimicrobial peptide selectively targets endosymbionts within the bacteriocytes and regulates their growth through the inhibition of cell division. Silencing the colA gene with RNA interference resulted in a decrease in size of the giant filamentous endosymbionts, which escaped from the bacteriocytes and spread into insect tissues. Although this family of peptides is commonly linked with microbe clearance, this work shows that endosymbiosis benefits from ColA, suggesting that long-term host-symbiont coevolution might have shaped immune effectors for symbiont maintenance.
TL;DR: Observations indicate that the normal human skin microflora protects skin via various modes of action, a conclusion supported by many lines of evidence associating diseases such as acne, atopic dermatitis, psoriasis and rosacea with an imbalance of the microFLora even in the absence of classical infection.
TL;DR: This review will focus on expression, function, regulation and functional efficacy of antimicrobial peptides against F. nucleatum, one of the most interesting gram-negative bacteria implicated in periodontal diseases.
Abstract: The pathogenesis of periodontitis involves the interplay of microbiota present in the subgingival plaque and the host responses Inflammation and destruction of periodontal tissues are considered to result from the response of a susceptible host to a microbial biofilm containing gram-negative pathogens Antimicrobial peptides are important contributors to maintaining the balance between health and disease in this complex environment These include several salivary antimicrobial peptides such as β-defensins expressed in the epithelium and LL-37 expressed in both epithelium and neutrophils Among gram-negative bacteria implicated in periodontal diseases, Fusobacterium nucleatum, is one of the most interesting This review will focus on expression, function, regulation and functional efficacy of antimicrobial peptides against F nucleatum We are looking for how the presence of F nucleatum induces secretion of peptides which have an impact on host cells and modulate immune response
TL;DR: Important roles for these novel cytokines in inflammatory skin diseases are suggested and these peptides are identified as potential targets for antipsoriatic therapies.
Abstract: IL-1F6, IL-1F8, and IL-1F9 and the IL-1R6(RP2) receptor antagonist IL-1F5 constitute a novel IL-1 signaling system that is poorly characterized in skin. To further characterize these cytokines in healthy and inflamed skin, we studied their expression in healthy control, uninvolved psoriasis, and psoriasis plaque skin using quantitative RT-PCR and immunohistochemistry. Expression of IL-1F5, -1F6, -1F8, and -1F9 were increased 2 to 3 orders of magnitude in psoriasis plaque versus uninvolved psoriasis skin, which was supported immunohistologically. Moreover, treatment of psoriasis with etanercept led to significantly decreased IL-1F5, -1F6, -1F8, and -1F9 mRNAs, concomitant with clinical improvement. Similarly increased expression of IL-1F5, -1F6, -1F8, and -1F9 was seen in the involved skin of two mouse models of psoriasis. Suggestive of their importance in inflamed epithelia, IL-1α and TNF-α induced IL-1F5, -1F6, -1F8, and -1F9 transcript expression by normal human keratinocytes. Microarray analysis revealed that these cytokines induce the expression of antimicrobial peptides and matrix metalloproteinases by reconstituted human epidermis. In particular, IL-1F8 increased mRNA expression of human β-defensin (HBD)-2, HBD-3, and CAMP and protein secretion of HBD-2 and HBD-3. Collectively, our data suggest important roles for these novel cytokines in inflammatory skin diseases and identify these peptides as potential targets for antipsoriatic therapies.
TL;DR: This review collates information regarding peptidic hydrolysates with antioxidant and antimicrobial properties isolated from vertebrate and invertebrate muscle and by-products, identifying the sources, the isolation and characterisation techniques used, and the methods used to demonstrate these bioactivities in vitro.
TL;DR: These groups of new peptides have creative medical and industrial application potentials to treat antibiotic-resistant bacterial infections and septic shock, to preserve food or to sanitise surfaces both in vitro and in vivo.
TL;DR: Treatment of influenza-infected individuals with cathelicidin-derived therapeutics, or modulation of endogenous cathe Licidin production may provide significant protection against disease, according to the severity of the disease and the effects of the peptides on disease.
Abstract: The extensive world-wide morbidity and mortality caused by influenza A viruses highlights the need for new insights into the host immune response and novel treatment approaches. Cationic Host Defense Peptides (CHDP, also known as antimicrobial peptides), which include cathelicidins and defensins, are key components of the innate immune system that are upregulated during infection and inflammation. Cathelicidins have immunomodulatory and anti-viral effects, but their impact on influenza virus infection has not been previously assessed. We therefore evaluated the effect of cathelicidin peptides on disease caused by influenza A virus in mice. The human cathelicidin, LL-37, and the murine cathelicidin, mCRAMP, demonstrated significant anti-viral activity in vivo, reducing disease severity and viral replication in infected mice to a similar extent as the well-characterized influenza virus-specific antiviral drug zanamivir. In vitro and in vivo experiments suggested that the peptides may act directly on the influenza virion rather than via receptor-based mechanisms. Influenza virus-infected mice treated with LL-37 had lower concentrations of pro-inflammatory cytokines in the lung than did infected animals that had not been treated with cathelicidin peptides. These data suggest that treatment of influenza-infected individuals with cathelicidin-derived therapeutics, or modulation of endogenous cathelicidin production may provide significant protection against disease.
TL;DR: The importance of the lipid composition of bacterial membranes in determining the susceptibility of the organism to the action of certain antimicrobial agents is emphasized.
Abstract: Many antimicrobial agents that target bacteria are cationic and can interact with the anionic lipid components that are exposed on the bacterial membrane. Bacteria vary widely in the nature of the major lipid components that are in the cell membrane. Those bacteria with both anionic as well as zwitterionic or neutral lipids can be induced to form domains in the presence of antimicrobial peptides possessing several cationic charges. This segregation of anionic and zwitterionic lipids into domains can result in the arrest of cell growth or in cell death. Such agents are generally more toxic to Gram-negative bacteria, than to Gram-positive ones. These findings emphasize the importance of the lipid composition of bacterial membranes in determining the susceptibility of the organism to the action of certain antimicrobial agents.
TL;DR: Understanding AMP structure-function relationship in the tethered conformation will enable rational improvements of immobilisation parameters and solve foreseeable challenges in the development of AMP-coated devices.
TL;DR: This review introduces their structure, classification, distribution, synthesis, and focuses on their biological activities and mechanisms, as well as clinical relevance, which have implications for the prevention and treatment of a variety of infectious diseases.
Abstract: The innate immune system is the first line of defense against many common microorganisms, which can initiate adaptive immune responses to provide increased protection against subsequent re-infection by the same pathogen. As a major family of antimicrobial peptides, defensins are widely expressed in a variety of epithelial cells and sometimes in leukocytes, playing an important role in the innate immune system due to their antimicrobial, chemotactic and regulatory activities. This review introduces their structure, classification, distribution, synthesis, and focuses on their biological activities and mechanisms, as well as clinical relevance. These studies of defensins in the innate immune system have implications for the prevention and treatment of a variety of infectious diseases, including bacterial ocular disease.
TL;DR: A review of commonly used fusion partners (e.g., solubility-enhancing, aggregation-promoting and self-cleavable carriers, etc.), cleavage methods and optimization options for antimicrobial peptides production in E. coli is presented in this paper.
TL;DR: This review was conducted to demonstrate the mode of action by which antimicrobial peptides combat multidrug-resistant bacteria and prevent biofilm formation and to introduce clinical uses of these compounds for chronic disease, medical devices, and oral health.
Abstract: Over the last decade, decreasing effectiveness of conventional antimicrobial-drugs has caused serious problems due to the rapid emergence of multidrug-resistant pathogens. Furthermore, biofilms, which are microbial communities that cause serious chronic infections and dental plaque, form environments that enhance antimicrobial resistance. As a result, there is a continuous search to overcome or control such problems, which has resulted in antimicrobial peptides being considered as an alternative to conventional drugs. Antimicrobial peptides are ancient host defense effector molecules in living organisms. These peptides have been identified in diverse organisms and synthetically developed by using peptidomimic techniques. This review was conducted to demonstrate the mode of action by which antimicrobial peptides combat multidrug-resistant bacteria and prevent biofilm formation and to introduce clinical uses of these compounds for chronic disease, medical devices, and oral health. In addition, combinations of antimicrobial peptides and conventional drugs were considered due to their synergetic effects and low cost for therapeutic treatment.
TL;DR: These findings strongly suggest that disruption of the cytoplasmic membrane is not the growth-halting mechanism, and enable dissection of antimicrobial design criteria into two parts: translocation across the OM and the subsequent halting of growth.
Abstract: Natural antimicrobial peptides (AMPs) provide prototypes for the design of unconventional antimicrobial agents. Existing bulk assays measure AMP activity but do not provide details of the growth-halting mechanism. We use fluorescence microscopy to directly observe the attack of the human antimicrobial peptide LL-37 on single Escherichia coli cells in real time. Our findings strongly suggest that disruption of the cytoplasmic membrane is not the growth-halting mechanism. At 8 μM, LL-37 binding saturates the outer membrane (OM) within 1 min. Translocation across the OM and access to the periplasmic space (5–25 min later) correlates in time with the halting of growth. Septating cells are attacked more readily than nonseptating cells. The halting of growth may occur because of LL-37 interference with cell wall biogenesis. Only well after growth halts does the peptide permeabilize the cytoplasmic membrane to GFP and the small dye Sytox Green. The assay enables dissection of antimicrobial design criteria into two parts: translocation across the OM and the subsequent halting of growth.
TL;DR: This review focuses on in vivo studies relating how organisms - bacteria, plants, insects and mammals - employ AMPs in their interactions with microbial competitors, pathogens and symbionts.
TL;DR: This review summarizes recent efforts in the development of peptide-based transport systems, such as cell-penetrating peptides (CPPs), which have come into focus and their efficiency has been demonstrated in many different applications.
Abstract: Antimicrobial peptides (AMPs) are a group of peptides that are active against a diverse spectrum of microorganisms. Due to their mode of action, AMPs are a promising class of molecules that could overcome the problems of increasing resistance of bacteria to conventional antibiotics. Furthermore, AMPs are strongly membrane-active and some are able to translocate into cells without the necessity for permanent membrane permeabilization. This feature has brought them into focus for use as transport vectors in the context of drug delivery. Since the plasma membrane restricts transport of bioactive substances into cells, great research interest lies in the development of innovative ways to overcome this barrier and to increase bioavailability. In this context, peptide-based transport systems, such as cell-penetrating peptides (CPPs), have come into focus, and their efficiency has been demonstrated in many different applications. However, more recently, also some AMPs have been used as efficient vectors for intracellular translocation of various active molecules. This review summarizes recent efforts in this interesting field of drug delivery. Moreover, some examples of the application of CPPs as efficient antimicrobial substances will be discussed.
TL;DR: Data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria.
Abstract: Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria.
TL;DR: The present review discusses two of the major classes of mammalian antimicrobial peptides: the defensins and the cathelicidins and focuses on their structures, their main modes of action and their regulation.
Abstract: Antimicrobial peptides are present in all walks of life, from plants to animals, and they are considered to be endogenous antibiotics. In general, antimicrobial peptides are determinants of the composition of the microbiota and they function to fend off microbes and prevent infections. Antimicrobial peptides eliminate micro-organisms through disruption of their cell membranes. Their importance in human immunity, and in health as well as disease, has only recently been appreciated. The present review provides an introduction to the field of antimicrobial peptides in general and discusses two of the major classes of mammalian antimicrobial peptides: the defensins and the cathelicidins. The review focuses on their structures, their main modes of action and their regulation.
TL;DR: Interestingly, commensal bacteria are able to amplify the innate immune response of human keratinocytes to pathogens by increased induction of AMP expression and abrogation of NF-κB suppression, suggesting that the two activation pathways can act in a synergistic way.