Role Of Antimicrobial Peptides Research Articles

The role of antimicrobial peptides in defending the urinary tract against infections

With antibiotic resistance increasing and new microbial resistance factors forming, the problem of creating new methods to treat and prevent the urinary tract infections becomes topical. The latest studies showed that urothelium contains a large number of immune factors providing its protection against the adverse effects of various uropathogens in vivo. There are very promising molecules – antimicrobial peptides (AMPs) – in terms of further therapeutic use among the components of inborn immunity. AMPs are the evolutionarily oldest molecules of innate immunity. The article discusses current data on the presence of various classes of AMPs in the urinary system, demonstrates data on their effectiveness as therapeutic agents against UTI, and describes further prospects for their use in the GP practice.

Expression of Psoriasin in Human Papillomavirus-Induced Cervical High-Grade Squamous Intraepithelial Lesions.

Persistent infection with human papillomavirus causes cervical high-grade squamous intraepithelial lesions (HSILs). The role of antimicrobial peptides (AMPs) in premalignant and malignant transformation is not fully understood. In this study, we examined the expression of human β-defensin 1 (HBD-1), HBD-2, HBD-3, LL37, psoriasin, and interleukin 8 (IL-8) in women with HSIL before and 6 months after surgery. Biopsies and secretion samples from the cervical canal were collected from 19 patients with HSIL and 14 healthy controls. The mRNA expression of HBD-1, HBD-2, HBD-3, LL37, psoriasin, and IL-8 was analyzed before and 6 months after surgery excision using reverse transcriptase real time polymerase chain reaction. For protein analyses, ELISA and immunohistochemistry were used for psoriasin and ELISA for IL-8. The mRNA expression of psoriasin was lower in patients before treatment compared with healthy controls (p = .05). After surgery, when the infection was cleared, psoriasin increased on mRNA (p = .04) and protein (p = .03) levels compared with before treatment. Immunostaining for psoriasin after treatment was prominent and localized in the cytoplasm of the epithelial cells. After treatment, IL-8 mRNA was reduced compared with before treatment (p = .05), but not on the protein level. No changes in mRNA expression of the other AMPs analyzed were observed in pretreatment and posttreatment samples. In this study of AMP expression in human papillomavirus-induced HSIL, we observed lower psoriasin levels before surgery compared with after treatment, when both mRNA and protein levels were similar to healthy controls. Interleukin 8, on the other hand, was increased before treatment, indicating an inflammatory response.

The role of antimicrobial peptides in the prevention of sexually transmitted infection (STI)

The role of antimicrobial peptides in the prevention of sexually transmitted infection (STI)

Beta defensin 3 enhances ovarian granulosa cell proliferation and migration via ERK1/2 pathway in vitro†.

Antimicrobial peptides (AMPs) are regarded as host defense peptides that possess bactericidal activity as well as immunomodulatory function. However, the role of AMP in the mammalian ovary is unknown. In the present study, porcine granulosa cells were utilized in a cell model to study the role of porcine beta defensin 2 (pBD2; pDEFB4B) and 3 (pBD3; pDEFB103A) during ovarian follicular development. Granulosa cells were cultured in the absence and presence of 1, 10, and 50μg/ml of pDEFB4B or pDEFB103A. After 24 h of treatment, pDEFB103A but not pDEFB4B stimulated granulosa cell proliferation in a concentration-dependent manner (P<0.05). This effect was dependent on the stage of follicular development. In addition, transwell cell migration assay showed that in the presence of pDEFB103A (10μg/ml), a 2.5-fold increase in cell migration was achieved. Furthermore, further study revealed that pDEFB103A increased the mRNA levels of cyclin D1 (CCND1) and proliferating cell nuclear antigen (PCNA), both associated with cell proliferation. To study the potential pathway involved in pDEFB103A-induced cell proliferation and migration, western blots were performed. It was found that pDEFB103A significantly increased the phosphorylated-ERK1/2 to nonphosphorylated ratio. Moreover, pretreatment with the U0126, a specific ERK1/2 phosphorylation inhibitor, suppressed PDEFB103A inducing GCs ERK1/2 phosphorylation, as well as proliferation and migration, suggesting that PDEFB103A may act via activating the ERK1/2 pathway. Furthermore, using a signal transduction pathway Elk-1 trans-reporting system, the activation of ERK1/2 pathway by PDEFB103A was further confirmed. Our data suggest that AMP may play a physiological role in the mammalian ovary.

The role of antimicrobial peptides in plant immunity.

Selective pressure imposed by millions of years of relentless biological attack has led to the development of an extraordinary array of defense strategies in plants. Among these, antimicrobial peptides (AMPs) stand out as one of the most prominent components of the plant immune system. These small and usually basic peptides are deployed as a generalist defense strategy that grants direct and durable resistance against biotic stress. Even though their name implies a function against microbes, the range of plant-associated organisms affected by these peptides is much broader. In this review, we highlight the advances in our understanding on the role of AMPs in plant immunity. We demonstrate that the capacity of plant AMPs to act against a large spectrum of enemies relies on their diverse mechanism of action and remarkable structural stability. The efficacy of AMPs as a defense strategy is evidenced by their widespread occurrence in the plant kingdom, an astonishing heterogeneity in host peptide composition, and the extent to which plant enemies have evolved effective counter-measures to evade AMP action. Plant AMPs are becoming an important topic of research due to their significance in allowing plants to thrive and for their enormous potential in agronomical and pharmaceutical fields.

Antimicrobial Peptides in Health and Disease (Review)

The review describes the latest data on the role of antimicrobial peptides (AMPs) in health and disease, as well as their structure and mechanisms of action. AMPs mediate protection by both direct lysis of bacteria and also by regulation of inflammation and chemotaxis, thus demonstrating immunomodulatory properties. A large amount of data shows that AMPs play an important role in the pathogenesis of multiple chronic diseases with genetic predisposition, such as atopic dermatitis, rosacea, and scleroderma.

Antimicrobial Peptides Secreted From Human Cryopreserved Viable Amniotic Membrane Contribute to its Antibacterial Activity

Chronic wounds remain a large problem in the field of medicine and are often associated with risk of infection and amputation. Recently, a commercially available human cryopreserved viable amniotic membrane (hCVAM) has been shown to effectively promote wound closure and reduce wound-related infections. A sprevious study indicates that hCVAM can inhibit the growth of bacteria associated with chronic wounds. In the present study, we investigated the mechanism of hCVAM antimicrobial activity. Our data demonstrate that antimicrobial activities against common pathogens in chronic wounds such as P.aeruginosa, S.aureus and Methicillin-resistant S.aureus (MRSA) are mediated via the secretion of soluble factors by viable cells in hCVAM and that these factors are proteins in nature. Further, we show that genes for antimicrobial peptides (AMPs) including human beta-defensins (HBDs) are expressed by hCVAM and that expression levels positively correlate with antimicrobial activity of hCVAM. At the protein level, our data indicate that HBD2 and HBD3 are secreted by hCVAM and directly contribute to its activity against P. aeruginosa. These data provide evidence that soluble factors including AMPs are hCVAM antimicrobial agents and are consistent with a role for AMPs in mediating antimicrobial properties of the membrane.

The investigation of antimicrobial peptides expression and its related interaction with methotrexate treatment in patients with psoriasis vulgaris

Background: Psoriasis is a chronic, inflammatory and immune-mediated disease. Recently, the role of antimicrobial peptides (AMPs) such as human beta defensins (hBDs) in the pathogenesis of psoriasis has been investigated. We aimed to evaluate the expression profiles of hBD-1 and hBD-2 in psoriatic skin before and after methotrexate (MTX) therapy and to compare healthy controls.Methods: Immunohistochemical expressions of hBD-1 and hBD-2 were assessed in 16 patients with psoriasis vulgaris and 20 normal skin biopsies from healthy controls. The patients were administered a 12 week of MTX and skin biopsy samples were obtained from the lesional skin of the patients pre-/posttreatment and normal body of the healthy controls.Results: The median (range) Psoriasis Area and Severity Index (PASI) value was 21.6 (8.2–27.7) before the treatment whereas; 3.05 (1–23.4) after the treatment. hBD-1 expression in psoriasis patients was significantly higher as compared to the healthy controls before treatment (p < 0.01). No significant difference was observed between psoriasis patients and healthy controls in terms of hBD-2 expression before treatment (p > 0.05). No significant difference was observed between before–after MTX treatment in terms of hBD-1 and hBD-2 expression levels in psoriasis patients (p > 0.05).Conclusions: These findings suggest a role for hBD-1 in psoriasis pathogenesis. But MTX treatment does not affect on hBD-1 and hBD-2 expressions. Further studies are needed to assess the roles of these AMPs in psoriasis etiopathogenesis.

The Role of Antimicrobial Peptides in Lung Cancer Therapy

Lung cancer is a major health burden accounting for 1.59 million deaths worldwide. For both sub-types of lung cancer (NSCLC and SCLC), chemotherapy is an option. However, success is limited and side effects are detrimental to an individuals’ overall quality of life. To complicate matters further, cancer cells can develop resistance to chemotherapeutic agents due to the presence of membrane associated proteins such as P-glycoprotein and Multidrug resistance-associated protein. Thus it is, imperative that new drug treatments are developed that have neither the toxicity nor mechanisms of resistance associated with conventional chemotherapy. In recent years, antimicrobial peptides (AMPs) have attracted attention as potential anti-cancer drugs due to reports that they can selectively target and kill cancer cells while leaving normal healthy cells unaffected. This review summaries several studies and discusses whether AMPs could be a viable treatment option in the fight against lung cancer.

The Role of Antimicrobial Peptides in Influenza Virus Infection and Their Potential as Antiviral and Immunomodulatory Therapy.

Influenza A virus (IAV) remains a major threat that can cause severe morbidity and mortality due to rapid genomic variation. Resistance of IAVs to current anti-IAV drugs has been emerging, and antimicrobial peptides (AMPs) have been considered to be potential candidates for novel treatment against IAV infection. AMPs are endogenous proteins playing important roles in host defense through direct antimicrobial and antiviral activities and through immunomodulatory effects. In this review, we will discuss the anti-IAV and immunomodulatory effects of classical AMPs (defensins and cathelicidins), and proteins more recently discovered to have AMP-like activity (histones and Alzheimer’s associated β-amyloid). We will discuss the interactions between AMPs and other host defense proteins. Major emphasis will be placed on novel synthetic AMPs derived from modification of natural proteins, and on potential methods of increasing expression of endogenous AMPs, since these approaches may lead to novel antiviral therapeutics.

Friend, foe or food? Recognition and the role of antimicrobial peptides in gut immunity and Drosophila-microbe interactions.

Drosophila melanogaster lives, breeds and feeds on fermenting fruit, an environment that supports a high density, and often a diversity, of microorganisms. This association with such dense microbe-rich environments has been proposed as a reason that D. melanogaster evolved a diverse and potent antimicrobial peptide (AMP) response to microorganisms, especially to combat potential pathogens that might occupy this niche. Yet, like most animals, D. melanogaster also lives in close association with the beneficial microbes that comprise its microbiota, or microbiome, and recent studies have shown that antimicrobial peptides (AMPs) of the epithelial immune response play an important role in dictating these interactions and controlling the host response to gut microbiota. Moreover, D. melanogaster also eats microbes for food, consuming fermentative microbes of decaying plant material and their by-products as both larvae and adults. The processes of nutrient acquisition and host defence are remarkably similar and use shared functions for microbe detection and response, an observation that has led to the proposal that the digestive and immune systems have a common evolutionary origin. In this manner, D. melanogaster provides a powerful model to understand how, and whether, hosts differentiate between the microbes they encounter across this spectrum of associations.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

Péptidos antimicrobianos y mediadores lipídicos: rol en las enfermedades periodontales

Currently, there is consensus that the damage of the tooth support tissues that occurs during periodontitis is a complex mechanism, in which the presence of specific periodontal pathogens is necessary, but not sufficient, to fully explain the extent and severity of the observed periodontal destruction. Moreover, the destruction of periodontal support tissue is largely the effect of the imbalance in the patient immune response, triggered by periodontal pathogen-derived antigens and virulence factors. The immune response elicited by periodontal pathogenic bacteria includes mechanisms associated with both innate and adaptive responses, where the role of antimicrobial peptides and lipid mediators are related to these two arms of immunity, and have not been fully elucidated in relation to their mechanisms of action against periodontal pathogens. In this review, a discussion is presented on the characteristics of these molecules and their role in periodontal disease in relation to both protection and destruction of tooth supporting tissue during periodontal infection. The relevance of considering these mediators within the complex scenario of the immune response during periodontal diseases is also highlighted, since they are a fundamental part of the host immune response. Periodontal diseases should be analysed in a broader perspective, where the study of these types of molecules involved in the immune response of periodontal tissues, may help to develop new therapeutic approaches to periodontal diseases in the future.

Potent Human α-Amylase Inhibition by the β-Defensin-like Protein Helianthamide.

Selective inhibitors of human pancreatic α-amylase (HPA) are an effective means of controlling blood sugar levels in the management of diabetes. A high-throughput screen of marine natural product extracts led to the identification of a potent (Ki = 10 pM) peptidic HPA inhibitor, helianthamide, from the Caribbean sea anemone Stichodactyla helianthus. Active helianthamide was produced in Escherichia coli via secretion as a barnase fusion protein. X-ray crystallographic analysis of the complex of helianthamide with porcine pancreatic α-amylase revealed that helianthamide adopts a β-defensin fold and binds into and across the amylase active site, utilizing a contiguous YIYH inhibitory motif. Helianthamide represents the first of a novel class of glycosidase inhibitors and provides an unusual example of functional malleability of the β-defensin fold, which is rarely seen outside of its traditional role in antimicrobial peptides.

Rola peptydów przeciwdrobnoustrojowych w wybranych dermatozach

Rola peptydów przeciwdrobnoustrojowych w wybranych dermatozach

The role of antimicrobial peptides in chronic inflammatory skin diseases.

Antimicrobial peptides (AMPs) are effector molecules of the innate immune system of the skin. They present an activity against a broad spectrum of Gram-positive and Gram-negative bacteria as well as some fungi, parasites and enveloped viruses. Several inflammatory skin diseases including psoriasis, atopic dermatitis, acne vulgaris and rosacea are characterized by a dysregulated expression of AMPs. Antimicrobial peptides are excessively produced in lesional psoriatic scales or rosacea in contrast to the atopic skin that shows lower AMP levels when compared with psoriasis. The importance of the AMPs contribution to host immunity is indisputable as alterations in the antimicrobial peptide expression have been associated with various pathologic processes. This review discusses the biology and clinical relevance of antimicrobial peptides expressed in the skin and their role in the pathogenesis of inflammatory skin diseases.

Small Peptides with a Big Role: Antimicrobial Peptides in the Pregnant Female Reproductive Tract.

There is a growing interest in the role of antimicrobial peptides (AMPs) in the female reproductive tract during pregnancy. This commentary highlights recent advances in the field including those of Itakoa and colleagues who have demonstrated elafin and secretory leukocyte protease inhibitor (SLPI) expression in cervical cells from pregnant women during pregnancy. They suggest that these specific AMPs may be raised in women in true preterm labour. This complements other studies exploring the use cervico-vaginal fluid elafin and other antimicrobial peptides as biomarkers to predict risk of spontaneous preterm birth early in pregnancy. With continued focus on the contribution and regulation of these important small peptides in pregnancy, the potential of AMPs as clinical tools for identifying women most at risk of spontaneous preterm birth should soon be realised.

Antimicrobial peptides in asthma pathogenesis

Antimicrobial peptides exhibit activity against bacteria, viruses, fungi, and parasites. They have been described not only as endogenous antibiotics but also as immune modulators with an impact on innate and adaptive immune functions. Asthma is one of the most common diseases, characterized by chronic airway inflammation, bronchial hyperreactivity and asthma attacks. Airway inflammation in asthma is characterized by allergic phenotypes, such as dense infiltration of eosinophils, mast cells, Th 2 lymphocytes and monocytes. Viral infections are often the cause of asthma exacerbation. This review highlights recent observations on the role of antimicrobial peptides in asthma pathogenesis.

Role of antimicrobial peptides in periodontal innate defense mechanism

The periodontal epithelium neighboring the tooth is precise to form a seal and attachment around the tooth. This exclusive function imparts unique challenges to the tissue and leads to certain vulnerabilities allied with periodontal disease, particularly in view of the continual exposure to the bacterial biofilm (dental plaque) that form that is formed on the tooth surface at the junction of the soft tissue. It is obvious that oral epithelial cells can counter unbroken microbial challenges from dental plaque by the production of antimicrobial peptides (AMPs), chemokines and cytokines that boost inflammation and immune response in periodontal tissues. AMPs are early responders of the innate immune system that search and destroy invading pathogens. The large variety of AMPs presumably allows for an effective response to the large variety of microorganisms that invade the mouth and airways. The present paper portrays the association between altered expression of AMPs and some types of periodontitis along with AMPs and their clinical significance in other oral diseases.

Antimicrobial peptides in the female reproductive tract: a critical component of the mucosal immune barrier with physiological and clinical implications.

At the interface of the external environment and the mucosal surface of the female reproductive tract (FRT) lies a first-line defense against pathogen invasion that includes antimicrobial peptides (AMP). Comprised of a unique class of multifunctional, amphipathic molecules, AMP employ a wide range of functions to limit microbial invasion and replication within host cells as well as independently modulate the immune system, dampen inflammation and maintain tissue homeostasis. The role of AMP in barrier defense at the level of the skin and gut has received much attention as of late. Given the far reaching implications for women's health, maternal and fetal morbidity and mortality, and sexually transmissible and polymicrobial diseases, we herein review the distribution and function of key AMP throughout the female reproductive mucosa and assess their role as an essential immunological barrier to microbial invasion throughout the reproductive cycle of a woman's lifetime. A comprehensive search in PubMed/Medline was conducted related to AMP general structure, function, signaling, expression, distribution and barrier function of AMP in the FRT, hormone regulation of AMP, the microbiome of the FRT, and AMP in relation to implantation, pregnancy, fertility, pelvic inflammatory disease, complications of pregnancy and assisted reproductive technology. AMP are amphipathic peptides that target microbes for destruction and have been conserved throughout all living organisms. In the FRT, several major classes of AMP are expressed constitutively and others are inducible at the mucosal epithelium and by immune cells. AMP expression is also under the influence of sex hormones, varying throughout the menstrual cycle, and dependent on the vaginal microbiome. AMP can prevent infection with sexually transmissible and opportunistic pathogens of the female reproductive tissues, although emerging understanding of vaginal dysbiosis suggests induction of a unique AMP profile with increased susceptibility to these pathogens. During pregnancy, AMP are key immune effectors of the fetal membranes and placenta and are dysregulated in states of intrauterine infection and other complications of pregnancy. At the level of the FRT, AMP serve to inhibit infection by sexually and vertically transmissible as well as by opportunistic bacteria, fungi, viruses, and protozoa and must do so throughout the hormone flux of menses and pregnancy. Guarding the exclusive site of reproduction, AMP modulate the vaginal microbiome of the lower FRT to aid in preventing ascending microbes into the upper FRT. Evolving in parallel with, and in response to, pathogenic insults, AMP are relatively immune to the resistance mechanisms employed by rapidly evolving pathogens and play a key role in barrier function and host defense throughout the FRT.

Novel Role of the Antimicrobial Peptide LL-37 in the Protection of Neutrophil Extracellular Traps against Degradation by Bacterial Nucleases

Neutrophil extracellular traps (NETs) have been described as a fundamental innate immune defence mechanism. They consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs) which are able to engulf and kill pathogens. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the function of LL-37 within NETs is still unknown because it loses its antimicrobial activity when bound to DNA in the NETs. Using immunofluorescence microscopy, we demonstrate that NETs treated with LL-37 are distinctly more resistant to S. aureus nuclease degradation than nontreated NETs. Biochemical assays utilising a random LL-37-fragment library indicated that the blocking effect of LL-37 on nuclease activity is based on the cationic character of the AMP, which facilitates the binding to neutrophil DNA, thus protecting it from degradation by the nuclease. In good correlation to these data, the cationic AMPs human beta defensin-3 and human neutrophil peptide-1 showed similar protection of neutrophil-derived DNA against nuclease degradation. In conclusion, this study demonstrates a novel role of AMPs in host immune defence: beside its direct antimicrobial activity against various pathogens, cationic AMPs can stabilise neutrophil-derived DNA or NETs against bacterial nuclease degradation.