Role Of Antimicrobial Peptides Research Articles

Role of antimicrobial peptide in fish immunity

Role of antimicrobial peptide in fish immunity

Antimicrobial skin peptides in premature infants: Comparison with term infants and impact of perinatal factors.

Preterm infants have an immature epidermis barrier function that may lead to an increased permeability to pathogens. On the surface of the human skin, antimicrobial peptides (AMPs) are important molecules of the innate immune system, have broad antimicrobial properties, and provide an essential role in integrity of the microbiome. Given the marked susceptibility of preterm infants to infection, we hypothesize a decreased expression of AMPs on the skin of preterm infants. In a prospective single-center study with 35 preterm and 20 term infants, we analyzed skin rinsing probes for the presence of the AMPs psoriasin (S100A7) and ribonuclease 7 (RNase 7) via enzyme-linked immunosorbent assay. Samples were taken from preterm infants < 34 0/7 weeks gestational age (mean ± SD gestational age, 28.8 ± 2.4 weeks) on days 0, 7, 14, and 28 after birth. Term infants (> 36 6/7 weeks) (controls) were washed on days 0 and 28. Psoriasin and RNase 7 were both expressed on skin of preterm and term infants and increased in concentration significantly over time. RNase 7 was more expressed in term infants on day 0 [preterm = 1.1 (0.7-2.9) vs. term = 2.0 (1.1-3.4) ng/ml, p = 0.017]. On day 28, premature infants showed higher values of psoriasin [preterm = 10.9 (5.6-14.2) vs. term = 6.3 (3.4-9.0) ng/ml, p < 0.001]. Notably, preterm infants with infectious or inflammatory context driven by histological proof of chorioamnionitis and early-onset or late-onset sepsis had higher concentrations of psoriasin as compared with non-affected preterm infants. After exclusion of infants with inflammatory hit, median concentrations of RNase 7 and psoriasin did not differ between preterm and full-term infants on days 0 and 28. Psoriasin and RNase 7 concentrations increase over time on the skin of newborn infants and seem to play a role in the first defense against infection. This is of particularly interest as the role of AMPs on a maturing skin microbiome and its possible new prevention strategies is unclear and needs to be determined.

Antimicrobial Peptides Mediate Apoptosis by Changing Mitochondrial Membrane Permeability

Changes in mitochondrial membrane permeability are closely associated with mitochondria-mediated apoptosis. Antimicrobial peptides (AMPs), which have been found to enter cells to exert physiological effects, cause damage to the mitochondria. This paper reviews the molecular mechanisms of AMP-mediated apoptosis by changing the permeability of the mitochondrial membrane through three pathways: the outer mitochondrial membrane (OMM), inner mitochondrial membrane (IMM), and mitochondrial permeability transition pore (MPTP). The roles of AMPs in inducing changes in membrane permeability and apoptosis are also discussed. Combined with recent research results, the possible application prospects of AMPs are proposed to provide a theoretical reference for the development of AMPs as therapeutic agents for human diseases.

Roles of Antimicrobial Peptides in Gynecological Cancers.

Antimicrobial peptides (AMPs) are essential components of the mucosal barrier of the female reproductive tract (FRT) and are involved in many important physiological processes, including shaping the microbiota and maintaining normal reproduction and pregnancy. Gynecological cancers seriously threaten women’s health and bring a heavy burden to society so that new strategies are needed to deal with these diseases. Recent studies have suggested that AMPs also have a complex yet intriguing relationship with gynecological cancers. The expression level of AMPs changes during tumor progression and they may act as promising biomarkers in cancer detection and prognosis prediction. Although AMPs have long been considered as host protective, they actually play a “double-edged sword” role in gynecological cancers, either tumorigenic or antitumor, depending on factors such as AMP and cancer types, as well as AMP concentrations. Moreover, AMPs are associated with chemoresistance and regulation of AMPs’ expression may alter sensitivity of cancer cells to chemotherapy. However, more work is needed, especially on the identification of molecular mechanisms of AMPs in the FRT, as well as the clinical application of these AMPs in detection, diagnosis and treatment of gynecological malignancies.

Impact of smoking on protein levels of beta-defensins in periodontal disease.

Antimicrobial peptides (AMPs) are important components of the host response against invading pathogens. In addition to their direct antimicrobial activity, they can also participate in the immune system modulation. However, the role of AMPs in the etiopathogenesis of periodontal disease and the risk factors that may influence their expression in the oral cavity are not fully understood. The aim of this study was to determine the impact of smoking on beta-defensin (hBD) 1 and 2 levels analyzing samples from periodontitis patients. Fifty patients with periodontitis, 25 smokers and 25 non-smokers, and 20 periodontally healthy patients were recruited. After periodontal clinical evaluation, gingival crevicular fluid (GCF) samples were collected from healthy sites of patients without periodontal disease and from healthy and diseased sites of patients with periodontitis. Peptides quantification was performed by sandwich ELISA technique. Smokers showed reduced GCF hBD 1 levels and increased hBD 2 levels compared to non-smokers in diseased sites (p <0.05). Higher levels of hBD 1 were observed in healthy sites of patients without periodontal disease than in healthy sites of patients with periodontitis (p<0.0001). Diseased sites of non-smokers presented higher levels of hBD 2 than healthy sites (p <0.05). These results reveal that protein levels of hBDs 1 and 2 can be impaired by cigarette smoking in the presence of periodontal disease.

Role of Antimicrobial Peptides in Treatment and Prevention of Mycobacterium Tuberculosis: A Review.

Tuberculosis (TB) is one of the leading cause of death worldwide, and the world is fighting with this global health emergency from the past 25 year. The current clinical interventions for the management of TB face a number of inherent challenges which includes low patient compliance due to the long therapy regimen, and emerging antimicrobial resistance. Therefore, there is an unmet need of new anti-TB therapeutic agent with enhanced safety profile, which can reduce the duration of therapy, enhanced bioavailability and efficacy against drug resistant forms of TB. Bacteriocins or anti microbial peptides (AMPs) occurring in microbes, human beings and other life forms have been investigated as host defense peptides. Structurally AMPs are short and ionized and play crucial role in innate immunity of host. Some AMPs can kill microbial infections directly while others function indirectly by altering the host defense mechanisms. Amidst rising issue of antibiotic resistance, AMPs are being tested in clinical research as potential antibiotics and novel therapeutics to fight against infections and non-infectious diseases. Studies have also highlighted the ability of AMPs to act against the bacteria spreading tuberculosis. The present review provides information on antimicrobial peptides, highlights their biological role, classification and mode of action in treatment and prevention of tuberculosis. It further mentions the prospects and challenges of developing peptides for their therapeutic applications against mycobacterium tuberculosis.

The Activity of Antimicrobial Peptides in Pediatric Celiac Disease.

BackgroundCeliac disease (CD) is an immune-mediated disorder of the gut in which innate and adaptive responses are involved. Antimicrobial peptides (AMPs) constitute an arsenal of innate immunity regulators of paramount importance in the gut. However, the role of AMPs in CD is unclear.AimsTo evaluate the levels of fecal β-defensin-2, fecal calprotectin (FC), and antibodies against bactericidal/permeability-increasing protein (BPI) in the serum of children with active CD and to compare them with those of healthy controls (HCs).MethodsWe examined 76 children with recently diagnosed CD between the age of 2–10 years (average age: 6.1 ± 1.2 years) and 32 HC (average age: 6.2 ± 3.8 years) in this study. We evaluated the level of fecal β-defensin-2 and FC levels in coprofiltrates, and the level of anti-BPI antibodies in blood serum. Correlation relationships between the parameters were assessed according to Pearson correlation coefficient.ResultsFecal β-defensin-2 concentration was greater in the CD group than in HC group, amounting to 99.6 ± 15.5 ng/mL and 64.0 ± 2.4 ng/mL, respectively (p < 0.02). The level of FC in the CD children was 35.4 ± 8.1 μg/g, while that in the control group was 19.1 ± 1.1 μg/g, (p < 0.05), representing a slightly increase. The concentration of anti-BPI antibodies in the CD and HC groups was 35.9 ± 10.1 U/mL and 5.2 ± 3.2 U/mL, respectively (p < 0.002). There was a strong and direct correlation between fecal β-defensin-2 and FC (r = 0.69), as well as a direct but weak relationship between fecal β-defensin-2 and anti-BPI antibodies (r = 0.35).ConclusionsOur data reinforce that fecal β-defensin-2 and anti-BPI antibodies are greatly increased in patients with active CD. These biomarkers may be components of epithelial innate immunity in the intestine, with each having a distinct functional role in intestinal6 mucosal defense.

Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers.

Diabetic foot ulcer (DFU) is a devastating complication, affecting around 15% of diabetic patients and representing a leading cause of non-traumatic amputations. Notably, the risk of mixed bacterial–fungal infection is elevated and highly associated with wound necrosis and poor clinical outcomes. However, it is often underestimated in the literature. Therefore, polymicrobial infection control must be considered for effective management of DFU. It is noteworthy that antimicrobial resistance is constantly rising overtime, therefore increasing the need for new alternatives to antibiotics and antifungals. Antimicrobial peptides (AMPs) are endogenous peptides that are naturally abundant in several organisms, such as bacteria, amphibians and mammals, particularly in the skin. These molecules have shown broad-spectrum antimicrobial activity and some of them even have wound-healing activity, establishing themselves as ideal candidates for treating multi-kingdom infected wounds. Furthermore, the role of AMPs with antifungal activity in wound management is poorly described and deserves further investigation in association with antibacterial agents, such as antibiotics and AMPs with antibacterial activity, or alternatively the application of broad-spectrum antimicrobial agents that target both aerobic and anaerobic bacteria, as well as fungi. Accordingly, the aim of this review is to unravel the molecular mechanisms by which AMPs achieve their dual antimicrobial and wound-healing properties, and to discuss how these are currently being applied as promising therapies against polymicrobial-infected chronic wounds such as DFUs.

The characteristics and roles of antimicrobial peptides as potential treatment for antibiotic-resistant pathogens: a review.

The emergence of antibiotic-resistant bacteria has become a significant and ever-increasing threat to global public health, increasing both morbidity and mortality rates, and the financial burden on health services. Infection by drug-resistant bacteria is anticipated to contribute to the demise of almost 10 million people by the year 2050 unless a competent and effective response is devised to engage with this issue. The emergence and spread of resistance are commonly caused by the excessive or inappropriate use of antibiotics and substandard pharmaceuticals. It arises when pathogens adapt to different conditions and develop self-defence mechanisms. Currently, novel antimicrobial peptides (AMPs) have been reported to be the sole cure for some clinical cases of infectious diseases such as sepsis and skin infections, although these agents may, on occasion, require administration together with an adjunctive low-dose antibiotic. Although AMPs are a promising alternative form of anti-microbial therapy and easily applied in the medical sector, they still have limitations that should not be taken lightly. Hence, this review explores the characteristics, advantages and disadvantages of AMPs for their potential in treating antibiotic-resistant pathogens.

The antimicrobial peptide S100A8/A9 produced by airway epithelium functions as a potent and direct regulator of macrophage phenotype and function.

BackgroundElevated counts of alveolar macrophages and attenuated phagocytic capacity are associated with chronic obstructive pulmonary disease (COPD). Factors governing macrophage phagocytosis are poorly understood. In this study we aimed to compare the influence of airway epithelial cell secretions from individuals with COPD and without COPD (non-COPD) on macrophage phagocytic activity, and the role of antimicrobial peptides (AMPs).MethodsSupernatants from non-COPD and COPD small airway epithelial cell (SAEC) cultures exposed to non-typeable Haemophilus influenzae (NTHi) were applied to human monocyte-derived macrophages (MDMs) to assess their influence on phagocytosis. SAECs were analysed for changes in AMP expression by quantitative reverse transcription PCR, and the influence of select AMPs on macrophage phenotype and function was assessed by flow cytometry and metabolic activity assay.ResultsSecretions from the apical and basolateral surface of NTHi-exposed SAECs from non-COPD donors elicited superior phagocytic capacity in MDMs. Moreover, NTHi exposure led to a rapid increase in the expression of a range of AMPs by non-COPD SAECs, but this response was delayed in COPD SAECs. We demonstrate that treatment with AMPs β-defensin 2 and S100 calcium binding protein A8/S100 calcium binding protein A9 (S100A8/A9) improved the phagocytic capacity of MDMs. In-depth analysis of the influence of S100A8/A9 on MDMs revealed a role for this AMP in macrophage phenotype and function. Furthermore, we show that the expression of S100A8 and S100A9 is directly regulated by WNT/β-catenin signalling, a known deregulated pathway in COPD.ConclusionIn conclusion, for the first time, we demonstrate that airway epithelium from patients with COPD has a reduced capacity to support the phagocytic function of macrophages in response to acute NTHi exposure, and we identify the WNT/β-catenin signalling-modulated and epithelium-derived S100A8/A9 as a potent regulator of macrophage phenotype and function.

The Role of Antimicrobial Peptides in Preterm Birth.

Antimicrobial peptides (AMPs) are short cationic amphipathic peptides with a wide range of antimicrobial properties and play an important role in the maintenance of immune homeostasis by modulating immune responses in the reproductive tract. As intra-amniotic infection and microbial dysbiosis emerge as common causes of preterm births (PTBs), a better understanding of the AMPs involved in the development of PTB is essential. The altered expression of AMPs has been reported in PTB-related clinical presentations, such as preterm labor, intra-amniotic infection/inflammation, premature rupture of membranes, and cervical insufficiency. Moreover, it was previously reported that dysregulation of AMPs may affect the pregnancy prognosis. This review aims to describe the expression of AMPs associated with PTBs and to provide new perspectives on the role of AMPs in PTB.

Protegrin-1 Regulates Porcine Granulosa Cell Proliferation via the EGFR-ERK1/2/p38 Signaling Pathway in vitro.

Antimicrobial peptides (AMPs) are traditionally known to be essential components in host defense via their broad activities against bacteria, fungi, viruses, and protozoa. Their immunomodulatory properties have also recently received considerable attention in mammalian somatic tissues of various species. However, little is known regarding the role of AMPs in the development and maturation of ovarian follicles. Protegrin-1 (PG-1) is an antimicrobial peptide which is known to have potent antimicrobial activity against both gram positive and negative bacteria. Here we report that the PG-1 is present in the porcine ovarian follicular fluid. Treatment of granulosa cell with PG-1 enhanced granulosa cell proliferation in a dose-dependent manner. This is accompanied by increased expression of cell-cycle progression-related genes such as cyclin D1(CCND1), cyclin D2 (CCND2), and cyclin B1(CCNB1). Additionally, Western blot analysis showed that PG-1 increased phosphorylated epidermal growth factor receptor (EGFR), and the phosphorylated-/total extracellular signal-regulated kinase (ERK)1/2 ratio. Pretreatment with either U0126, a specific ERK1/2 phosphorylation inhibitor, or EGFR kinase inhibitor, AG1478, blocked the PG-1 induced proliferation. Moreover, luciferase reporter assay revealed that ETS domain-containing protein-1 (Elk1) C/EBP homologous protein (CHOP), and the transcription activators downstream of the MAPK pathway, were activated by PG-1. These data collectively suggest that PG-1 may regulate pig granulosa cell proliferation via EGFR-MAPK pathway., Hence, our finding offers insights into the role of antimicrobial peptides on follicular development regulation.

The role of antimicrobial peptides in the evolution of endosymbiotic protein import.

Antimicrobial peptides (AMPs) represent an ancient mechanism for antagonizing microbial opponents, being generated by eukaryotes, eubacteria, and archaea alike [1,2]. Given the dearth in new antibiotics, there has been increasing interest in AMPs. As our understanding has grown, a tantalizing possibility has taken shape: Might these agents of competition be at the heart of the cooperative success story that gave rise to mitochondria and chloroplasts? Striking similarities suggest that the system of protein import into these endosymbiotic organelles may derive from an interplay of AMP attack and defense [3].

Role of Antimicrobial Peptides in Skin Barrier Repair in Individuals with Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that exhibits a complex interplay of skin barrier disruption and immune dysregulation. Patients with AD are susceptible to cutaneous infections that may progress to complications, including staphylococcal septicemia. Although most studies have focused on filaggrin mutations, the physical barrier and antimicrobial barrier also play critical roles in the pathogenesis of AD. Within the physical barrier, the stratum corneum and tight junctions play the most important roles. The tight junction barrier is involved in the pathogenesis of AD, as structural and functional defects in tight junctions not only disrupt the physical barrier but also contribute to immunological impairments. Furthermore, antimicrobial peptides, such as LL-37, human β-defensins, and S100A7, improve tight junction barrier function. Recent studies elucidating the pathogenesis of AD have led to the development of barrier repair therapy for skin barrier defects in patients with this disease. This review analyzes the association between skin barrier disruption in patients with AD and antimicrobial peptides to determine the effect of these peptides on skin barrier repair and to consider employing antimicrobial peptides in barrier repair strategies as an additional approach for AD management.

Expression and Roles of Antimicrobial Peptides in Innate Defense of Airway Mucosa: Potential Implication in Cystic Fibrosis.

The treatment of respiratory infections is associated with the dissemination of antibiotic resistance in the community and clinical settings. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides (AMPs), the central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. Most AMPs are epithelium-derived and play a key role in host defense at mucosal surfaces. They are classified on the basis of their structure and amino acid motifs. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils, in particular, contribute to AMP synthesis. The relevance of AMPs for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Of note, AMPs are active against bacterial strains that are resistant to conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of AMPs. In this review, we focus on studies related to direct bactericidal effects of AMPs and their potential clinical applications with a particular focus on cystic fibrosis.

Honey Bee Suppresses the Parasitic Mite Vitellogenin by Antimicrobial Peptide.

The negative effects of honey bee parasitic mites and deformed wing virus (DWV) on honey bee and colony health have been well characterized. However, the relationship between DWV and mites, particularly viral replication inside the mites, remains unclear. Furthermore, the physiological outcomes of honey bee immune responses stimulated by DWV and the mite to the host (honey bee) and perhaps the pathogen/parasite (DWV/mite) are not yet understood. To answer these questions, we studied the tripartite interactions between the honey bee, Tropilaelaps mercedesae, and DWV as the model. T. mercedesae functioned as a vector for DWV without supporting active viral replication. Thus, DWV negligibly affected mite fitness. Mite infestation induced mRNA expression of antimicrobial peptides (AMPs), Defensin-1 and Hymenoptaecin, which correlated with DWV copy number in honey bee pupae and mite feeding, respectively. Feeding T. mercedesae with fruit fly S2 cells heterologously expressing honey bee Hymenoptaecin significantly downregulated mite Vitellogenin expression, indicating that the honey bee AMP manipulates mite reproduction upon feeding on bee. Our results provide insights into the mechanism of DWV transmission by the honey bee parasitic mite to the host, and the novel role of AMP in defending against mite infestation.

Detecting antimicrobial peptides by exploring the mutual information of their sequences

The rise of antibiotic resistance in pathogenic bacteria is a growing concern for every part of the world. The present study shows the prediction efficiency of mutual information for the classification of antimicrobial peptides. The proven role of antimicrobial peptides (AMPs) to fight against multidrug-resistant pathogens and AMP’s low toxic properties laid the foundation of computational methods to play their role in detecting AMPs from non-AMPs. Mutual information vectors (MIV) were created for AMP/non-AMP sequences and then fed to different machine learning classifiers out of which a random forest (RF) classifier showed best results for predicting AMPs. Random forest classifiers were evaluated on benchmark datasets by 10-fold cross-validation. The proposed MIV-RF method showed better prediction accuracy, MCC (Matthews correlation coefficient), and AUC-ROC (Area Under The Curve-Receiver Operating Characteristics) than available methods for detecting AMPs.Communicated by Ramaswamy H. Sarma

Induction of Antimicrobial Peptides in the Hemolymph of Spodoptera littoralis Larvae Following Treatment with Salmonella typhimurium

This study investigated the efficiency of intrahaemocoelic injection of sublethal concentration (LC20 = 5.7×103 cells/ml) of Salmonella typhimurium in the induction of immune response in 5th larval instar of Spodoptera littoralis. The role of antimicrobial peptides (AMPs) induced in the larval hemolymph was examined as natural antibiotics against different Gram-negative (G-ve) or Gram-positive (G+ve) bacteria. Where the larval plasma injected with Salmonella showed a significant antimicrobial activity against different strains of pathogenic bacteria (Staphylococcus aureus, Salmonella typhimurium, Escherichia coli and Enterococcus faecalis). The biochemical characterization of the immune hemolymph indicated drastic changes in both the total protein content and the protein banding patterns following bacterial injection. The total hemolymph proteins (THPs)decreased significantly 48 h post-Salmonella-injection. The hemolymph proteins profile was also qualitatively changed through the induction of new proteins and the disappearance of others simultaneously, which may be attributed to their participation in the immune reactions. The appearance of six new synthesized protein bands that were found to be specific for Salmonella injection, with a characteristic band of MW ~22 KDa predicting that this protein band may be Attacin-like AMP.

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.