Antimicrobial Peptides Research Articles

Activity of protegrin-1 against mouse Ehrlich ascites carcinoma <i>in vitro</i> and <i>in vivo</i>

BACKGROUND: The problem of multidrug resistance in cancer treatment creates an urgent demand for developing new effective antitumor agents. Due to the unusual mechanism of recognizing and damaging tumor cells, antimicrobial peptides are considered as possible prototypes for designing such therapeutics. AIM: This work was aimed to compare the antitumor potential of the promising membranolytic antimicrobial peptide protegrin-1 in vitro and in vivo in Ehrlich ascites carcinoma mice model. MATERIALS AND METHODS: We used two variants of the model by inducing a tumor in solid or ascites form. In the first case, the mice were injected with the peptide twice a week for three weeks, and in the second injections were provided every other day for six days. The activity of antimicrobial peptides against isolated Ehrlich ascites carcinoma cells in vitro was analyzed using MTT-test. RESULTS: Protegrin-1 demonstrated high activity against Ehrlich ascites carcinoma cells in vitro, but had no significant effect on the lifespan of mice bearing solid or ascites form of Ehrlich tumor at the dosing and administration regimens we used. However, treatment with protegrin-1 caused a decrease in the ascites volume and in the number of cells in the ascites fluid. CONCLUSIONS: Protegrin-1 retains its antitumor properties in vivo, but it may be presumed, that to effectively suppress tumor growth it requires a more frequent and prolonged administration compared with conventional antitumor antibiotics, of which we adopted the administration regimen for protegrin-1 in this study.

Directed modification of characteristics of syntetyc analogue of proline-rich peptide ChBac3.4 through dendrimerisation

BACKGROUND: According to the World Health Organization, microbial resistance to antibiotics is one of the most serious threats to human health, food safety and economic development. Antimicrobial peptides of animal origin, to which resistance is difficult to develop, appear to be a promising option to overcome this problem. To solve one of the problems in the practical use of peptides — their rapid degradation in blood plasma — dendrimerization of linear analogues of already existing antimicrobial peptides can be used. This work shows that dendrimers of shortened analogue of the natural proline-rich peptide ChBac3.4 are superior in antimicrobial activity to the original peptide and are much more stable in blood serum. At the same time, as the original peptide, branched analogues do not have hemolytic activity. AIM: The aim of this study is to develop new structural analogues of a peptide that have improved stability in blood serum while maintaining high antimicrobial activity. To achieve this, we intend to create dendrimeric (branched) molecules by synthesizing peptides using solid-phase methods. MATERIALS AND METHODS: We will investigate the antimicrobial properties of the peptides using the method of serial dilutions in a liquid nutrient medium against both Gram-positive and Gram-negative bacteria. We will also assess the stability of the peptides by culturing them in the presence of human blood serum. RESULTS: After making modifications to the original peptide, we expect to see a significant increase in its antimicrobial activity against all strains tested. Additionally, we anticipate that the resistance of these peptides will increase many times over. CONCLUSIONS: Overall, our findings suggest that dendrimerization can effectively improve the properties of proline-rich peptides, making them more suitable for use in medical applications.

Effects of Chicken Egg Powder, Bovine Colostrum, and Combination Therapy for the Treatment of Gastrointestinal Disorders

Natural-based products are of interest to the pharmaceutical industry as potential sources of novel medicinal compounds. They are also used by consumers/patients as standalone therapies or as an adjunct to Western medicines. Two natural-based products of interest are chicken egg and bovine colostrum (the milk produced in the first few days following calving). Both products are rich in immunoglobulins, antimicrobial peptides, growth factors, and macro- and micro-nutrients. In vitro, in vivo, and a limited number of clinical studies suggest therapeutic benefits of both components given alone and together. Combination therapy is of particular interest, as preclinical studies suggest synergistic effects on growth, repair, and gut protection, including microbiome-induced damage. This article describes the main constituents of egg and bovine colostrum, studies of their use alone and together for a wide range of conditions, highlights areas requiring further research, and describes novel indications such as GLP-1-associated gut symptoms. While well placed in the food supplement arena, additional high-quality clinical trials are required to establish their benefits in clinical practice.

ISOLATION AND MOLECULAR IDENTIFICATION OF INDIGENOUS BACTERIOCIN-PRODUCING WEISSELLA CIBARIA

Globally, over 6.22 million deaths are associated with antibiotic resistance. Bacteriocins, a set of antimicrobial peptides synthesized on the ribosomes, are widely viewed as a potential answer to this issue. This is due to their pore-forming ability and antimicrobial activity against antibiotic-resistant pathogens. The aim of this study is to isolate bacteriocin-producing Weissella cibaria and evaluate its antimicrobial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Salmonella typhi, Proteus mirabilis, Streptococcus sp., Candida sp. and Rhizopus stolonifer. Weissella cibaria man1 was isolated by inoculating deMan Rogosa Sharpe (MRS) broth with small pieces of ripe Mangifera indica (mango), 24-hour incubation at 370C, 10-fold serial dilution and plating on MRS agar. Molecular identification was achieved by DNA extraction, amplification of the 16S rRNA gene through polymerase chain reaction (PCR), agarose gel electrophoresis, gene sequencing, and BLASTN homology searches in the National Center for Biotechnology Information (NCBI). Antimicrobial activity of the bacteriocin was determined by agar well diffusion assay. Mangifera indica (mango) was found to harbor bacteriocin-producing Weissella cibaria man1. The bacteriocin (weissellicin man1) exhibited a broad spectrum of antimicrobial activity. Weissellicin man1 suppressed the growth of several target pathogens (Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus mirabilis, Candida sp. and Rhizopus stolonifer) but had no inhibitory action against Escherichia coli, Streptococcus sp., Staphylococcus aureus. In conclusion, weissellicin man1 from Weissella cibaria man1 has a broad-spectrum of antimicrobial action. These findings will facilitate further evaluation of the antimicrobial potency of weissellicin man1.

Novel Tree Shrew-Derived Antimicrobial Peptide with Broad-Spectrum Antibacterial Activity

Novel Tree Shrew-Derived Antimicrobial Peptide with Broad-Spectrum Antibacterial Activity

Molecular and energetic analysis of the interaction and specificity of Maximin 3 with lipid membranes: In vitro and in silico assessments.

In this study, the interaction of antimicrobial peptide Maximin 3 (Max3) with three different lipid bilayer models was investigated to gain insight into its mechanism of action and membrane specificity. Bilayer perturbation assays using liposome calcein leakage dose-response curves revealed that Max3 is a selective membrane-active peptide. Dynamic light scattering recordings suggest that the peptide incorporates into the liposomal structure without producing a detergent effect. Langmuir monolayer compression assays confirmed the membrane inserting capacity of the peptide. Attenuated total reflection-Fourier transform infrared spectroscopy showed that the fingerprint signals of lipid phospholipid hydrophilic head groups and hydrophobic acyl chains are altered due to Max3-membrane interaction. On the other hand, all-atom molecular dynamics simulations (MDS) of the initial interaction with the membrane surface corroborated peptide-membrane selectivity. Peptide transmembrane MDS shed light on how the peptide differentially modifies lipid bilayer properties. Molecular mechanics Poisson-Boltzmann surface area calculations revealed a specific electrostatic interaction fingerprint of the peptide for each membrane model with which they were tested. The data generated from the in silico approach could account for some of the differences observed experimentally in the activity and selectivity of Max3.

Membrane Fusion Mediated by Cationic Helical Peptide L-MMBen through Phosphatidylglycerol Recruitment.

Membrane fusion is the basis for many biological processes, which holds promise in biomedical applications including the creation of engineered hybrid cells and cell membrane functionalization. Extensive research efforts, including investigations into DNA zippers and carbon nanotubes, have been dedicated to the development of membrane fusion strategies inspired by natural SNARE proteins; nevertheless, achieving a delicate balance between membrane selectivity and high fusion efficiency through precise molecular engineering remains unclear. In our recent study, we successfully designed L-MMBen, a cationic helical antimicrobial peptide that exhibits remarkable antimicrobial efficacy while demonstrating moderate cytotoxicity. In this work, we demonstrate the effective and selective induction of fusion between phosphatidylglycerol (PG)-containing membranes by L-MMBen. By combining biophysical assays at the single-vesicle level with computer simulations at the molecular level, we discovered that L-MMBen can stably adsorb onto the surface of PG-containing membranes, leading to the formation of stalk structures between vesicles and ultimately resulting in membrane fusion. Furthermore, the occurrence of fusion is attributed to the unique ability of L-MMBen to recruit PG lipids and bridge adjacent vesicles. In contrast, its nonhelical counterpart DL-MMBen was found to lack this capability despite possessing an identical positive charge. These findings present an alternative molecule for achieving selective membrane fusion and provide insights for designing helical peptides with diverse applications.

Caerin 1.1 and 1.9 peptides halt B16 melanoma metastatic tumours via expanding cDC1 and reprogramming tumour macrophages

BackgroundCancer immunotherapy, particularly immune checkpoint inhibitors (ICBs) such as anti-PD-1 antibodies, has revolutionised cancer treatment, although response rates vary among patients. Previous studies have demonstrated that caerin 1.1 and 1.9, host-defence peptides from the Australian tree frog, enhance the effectiveness of anti-PD-1 and therapeutic vaccines in a murine TC-1 model by activating tumour-associated macrophages intratumorally.MethodsWe employed a murine B16 melanoma model to investigate the therapeutic potential of caerin 1.1 and 1.9 in combination with anti-CD47 and a therapeutic vaccine (triple therapy, TT). Tumour growth of caerin-injected primary tumours and distant metastatic tumours was assessed, and survival analysis conducted. Single-cell RNA sequencing (scRNAseq) of CD45+ cells isolated from distant tumours was performed to elucidate changes in the tumour microenvironment induced by TT.ResultsThe TT treatment significantly reduced tumour volumes on the treated side compared to untreated and control groups, with notable effects observed by Day 21. Survival analysis indicated extended survival in mice receiving TT, both on the treated and distant sides. scRNAseq revealed a notable expansion of conventional type 1 dendritic cells (cDC1s) and CD4+CD8+ T cells in the TT group. Tumour-associated macrophages in the TT group shifted toward a more immune-responsive M1 phenotype, with enhanced communication observed between cDC1s and CD8+ and CD4+CD25+ T cells. Additionally, TT downregulated M2-like macrophage marker genes, particularly in MHCIIhi and tissue-resident macrophages, suppressing Cd68 and Arg1 expression across all macrophage types. Differential gene expression analysis highlighted pathway alterations, including upregulation of oxidative phosphorylation and MYC target V1 in Arg1hi macrophages, and activation of pro-inflammatory pathways in MHCIIhi and tissue-resident macrophages.ConclusionOur findings suggest that caerin 1.1 and 1.9, combined with immunotherapy, effectively modulate the tumour microenvironment in primary and secondary tumours, leading to reduced tumour growth and enhanced systemic immunity. Further investigation into these mechanisms could pave the way for improved combination therapies in advanced melanoma treatment.

In-silico and in-vitro study of novel antimicrobial peptide AM1 from Aegle marmelos against drug-resistant Staphylococcus aureus

Antimicrobial peptides have garnered increasing attention as potential alternatives due to their broad-spectrum antimicrobial activity and low propensity for developing resistance. This is for the first time; proteome sequences of Aegle marmelos were subjected to in-silico digestion and AMP prediction were performed using DBAASP server. After screening the peptides on the basis of different physiochemical property, peptide sequence GKEAATKAIKEWGQPKSKITH (AM1) shows the maximum binding affinity with − 10.2 Kcal/mol in comparison with the standard drug (Trimethoprim) with − 7.4 kcal/mol and − 6.8 Kcal/mol for DHFR and SaTrmK enzyme respectively. Molecular dynamics simulation performed for 300ns, it has been found that peptide was able to stabilize the protein more effectively, analysed by RMSD, RMSF, and other statistical analysis. Free binding energy for DHFR and SaTrmK interaction from MMPBSA analysis with peptide was found to be -47.69 and − 44.32 Kcal/mol and for Trimethoprim to be -13.85 Kcal/mol and − 11.67 Kcal/mol respectively. Further in-vitro study was performed against Methicillin Susceptible Staphylococcus aureus (MSSA), Methicillin Resistant Staphylococcus aureus (MRSA), Multi-Drug Resistant Staphylococcus aureus (MDR-SA) strain, where MIC values found to be 2, 4, and 8.5 µg/ml lesser in comparison to trimethoprim which has higher MIC values 2.5, 5, and 9.5 µg/ml respectively. Thus, our study provides the insight for the further in-vivo study of the peptides against multi-drug resistant S. aureus.

Combined Phase 1/2a Initial Clinical Safety Trials and Proof-of-Concept Assessment of a Novel Antimicrobial Peptide KSL-W Anti-Plaque Chewing Gum.

The effective control of dental plaque is crucial for oral health, given that pathogenic bacteria in plaque are the primary cause of dental caries. Current antimicrobial agents, although effective, disrupt the oral microbiome and lead to oral dysbiosis, hindering efforts to curb dental caries. Novel antimicrobial peptides offer a promising solution due to their selective bactericidal activity against cariogenic bacteria. This study explores the initial safety and efficacy of KSL-W formulated into chewing gum through a Phase 1 and 2a clinical trial. The combined trial, approved by the FDA, follows a double-blind, randomized, placebo-controlled design. Phase 1 assessed safety with single doses (2-100 mg), whereas Phase 2a explored both safety and proof of concept in reducing oral bacteria with multiple doses (4-75 mg). Besides adverse events (Phase 1), outcome measures included whole-mouth plaque and gingival index scores and bleeding on probing (Phase 2a). KSL-W demonstrated safety in both phases, with no severe adverse events. The proof-of-concept analysis revealed a decrease in plaque and gingival inflammation, particularly at doses ≥ 20 mg. The 30 mg dose appeared to yield optimal effects without any adverse reactions in subjects. Results from this study indicate that KSL-W is safe for use in humans and provides initial evidence of its potential efficacy in reducing plaque and gingival inflammation. Further research is essential to determine optimal usage and ultimate safety, and to assess its potential in diverse populations. The trial is registered with the FDA (Trial Registration Number: NCT01877421). The clinical trials were registered in the clinicaltrials.gov database under the title "Safety and Tolerability of Antiplaque Chewing Gum in a Gingivitis Population" and the identifier number is NCT01877421. The URL for accessing the study in clinicaltrials.gov is https://clinicaltrials.gov/study/NCT01877421?intr=Antiplaque%20chewing&rank=1.

Bitter taste receptors as sensors of gut luminal contents.

Taste is important in the selection of food and is orchestrated by a group of distinct receptors, the taste G protein-coupled receptors (GPCRs). Taste 1 receptors (Tas1rs in mice and TAS1Rs in humans; also known as T1Rs) detect sweet and umami tastes, and taste 2 receptors (Tas2rs in mice and TAS2Rs in humans; also known as T2Rs) detect bitterness. These receptors are also expressed in extraoral sites, including the gastrointestinal mucosa. Tas2rs/TAS2Rs have gained interest as potential targets to prevent or treat metabolic disorders. These bitter taste receptors are expressed in functionally distinct types of gastrointestinal mucosal cells, including enteroendocrine cells, which, upon stimulation, increase intracellular Ca2+ and release signalling molecules that regulate gut chemosensory processes critical for digestion and absorption of nutrients, for neutralization and expulsion of harmful substances, and for metabolic regulation. Expression of Tas2rs/TAS2Rs in gut mucosa is upregulated by high-fat diets, and intraluminal bitter 'tastants' affect gastrointestinal functions and ingestive behaviour through local and gut-brain axis signalling. Tas2rs/TAS2Rs are also found in Paneth and goblet cells, which release antimicrobial peptides and glycoproteins, and in tuft cells, which trigger type 2 immune response against parasites, thus providing a direct line of defence against pathogens. This Review will focus on gut Tas2r/TAS2R distribution, signalling and regulation in enteroendocrine cells, supporting their role as chemosensors of luminal content that serve distinct functions as regulators of body homeostasis and immune response.

Thiazoplanomicin, a new thiazolyl peptide antibiotic from the leaf-litter actinomycete Actinoplanes sp. MM794L-181F6.

A new bioactive substance was identified from a leaf-litter actinomycete strain by screening for antibacterial activity against Neisseria gonorrhoeae. The thiazolyl peptide antibiotic, named thiazoplanomicin, was isolated from the secondary metabolites of the leaf-litter actinomycetes Actinoplanes sp. MM794L-181F6 by extraction with n-butanol, silica gel column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Thiazoplanomicin was characterized by LC-HR-ESI-MS, NMR, and X-ray analyses, along with analysis of the degradation products and chemical derivatives, and determined to be a nocathiacin-like multiple macrocyclic thiazolyl peptide. Thiazoplanomicin showed potent antimicrobial activity against gonococcal strains, including those resistant to known anti-gonococcal compounds such as telithromycin, azithromycin, and ceftriaxone, with MIC values ranging from 0.0312 to 0.125 µg ml-1. Such anti-gonococcal activity has not been reported on nocathiacin-like thiazolyl peptide antibiotic so far. Similar to other thiazolyl peptide antibiotics, thiazoplanomicin also showed potent antibacterial activity against Gram-positive bacteria with MIC values ranging from 0.0005 to 0.0156 µg ml-1 but showed no antibacterial activity against Escherichia coli.

Efflux Pump Inhibitors as a Broad-Spectrum Strategy to Combat Multidrug Resistance Acenitobacter Baumanii

The World Health Organization (WHO) identifies A. baumannii as one of the most resistant pathogens. Over the past few years, there has been a significant rise in its resistance to a wide array of antibiotics. Multidrug resistance is attributed to several mechanisms, with efflux pumps being the most notable. Recently, the development of new treatment strategies to tackle A. baumannii infections has shown great promise. This review focuses on the various families of efflux pumps in A. baumannii and explores innovative therapeutic options that have emerged over the past four years. Specifically, we emphasize synthetic and natural efflux pump inhibitors (EPIs), nanoparticles, bacteriophage therapy, and antimicrobial peptides (AMPs) as part of these novel strategies.

Antimicrobial Potential of Scorpion-Venom-Derived Peptides

The frequent and irrational use of antibiotics by humans has led to the escalating rise of antimicrobial resistance (AMR) with a high rate of morbidity-mortality worldwide, which poses a challenge to the development of effective treatments. A large number of host defense peptides from different organisms have gained interest due to their broad antibacterial spectrum, rapid action, and low target resistance, implying that these natural sources might be a new alternative to antimicrobial drugs. As important effectors of prey capture, defense against other animal attacks, and competitor deterrence, scorpion venoms have been developed as important candidate sources for modern drug development. With the rapid progress of bioanalytical and high throughput sequencing techniques, more and more scorpion-venom-derived peptides, including disulfide-bridged peptides (DBPs) and non-disulfide-bridged peptides (NDBPs), have been recently identified as having massive pharmacological activities in channelopathies, pathogen infections, and cancer treatments. In this review, we summarize the molecular diversity and corresponding structural classification of scorpion venom peptides with antibacterial, antifungal, and/or antiparasitic activity. We also aim to improve the understanding of the underlying mechanisms by which scorpion-venom-derived peptides exert these antimicrobial functions, and finally highlight their key aspects and prospects for antimicrobial therapeutic or pharmaceutical application.

The Variability of the Salivary Antimicrobial Peptide Profile: Impact of Lifestyle

Saliva is crucial in maintaining oral health; its composition reflects the body’s physiological and diseased state. Among salivary components, antimicrobial peptides (AMPs) stand out for their broad antimicrobial activities and role in modulating the oral microbiota and innate immune response. Local and systemic diseases can affect the levels of AMPs in saliva, making them attractive biomarkers. However, the large variability in their concentrations hampers their use in diagnostics. Knowledge of the various factors influencing the profile of salivary AMPs is essential for their use as biomarkers. Here, we examine how lifestyle factors such as physical activity, dietary supplementation, tobacco smoking, and psychological stress impact salivary AMP levels. By understanding these sources of variability, we can take a step forward in using AMPs for diagnostics and prognostics and develop new tailored and preventative approaches.

CRISPR-Cas system positively regulates virulence of Salmonella enterica serovar Typhimurium

BackgroundSalmonella, a foodborne pathogen, possesses a type I-E clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated (Cas) system. We investigated the system’s role in regulating Salmonella virulence by deleting the CRISPR arrays and Cas operon.ResultsOur study demonstrates invasion and proliferation defects of CRISPR-Cas knockout strains in intestinal epithelial cells and macrophages owing to the repression of invasion and virulence genes. However, proliferation defects were not observed in the Gp91phox−/− macrophages, suggesting the system’s role in the pathogens’ antioxidant defense. We deduced that the CRISPR-Cas system positively regulates H2O2 importer (OmpW), catalase (katG), peroxidase (ahpC), and superoxide dismutase (soda and sodCI), thereby protecting the cells from oxidative radicals. The knockout strains were attenuated in in-vivo infection models (Caenorhabditis elegans and BALB/c mice) due to hypersensitivity against antimicrobial peptides, complement proteins, and oxidative stress. The attenuation in virulence was attributed to the suppression of LPS modifying (pmr) genes, antioxidant genes, master regulators, and effectors of the SPI-1 (invasion) and SPI-2 (proliferation) islands in knockout strains. The regulation could be attributed to the partial complementarity of the CRISPR spacers with these genes.ConclusionsOverall, our study extends our understanding of the role of the CRISPR-Cas system in Salmonella pathogenesis and its virulence determinants.

Increased Lipocalin 2 detected by RNA sequencing regulates apoptosis and ferroptosis in COPD

BackgroundChronic obstructive pulmonary disease (COPD) is a complex respiratory condition influenced by environmental and genetic factors. Using next-generation sequencing, we aimed to identify dysregulated genes and potential therapeutic targets for COPD.MethodsPeripheral blood leukocyte RNA profiles from COPD patients and healthy controls were analyzed using next-generation sequencing. Key genes involved in COPD pathogenesis were identified through protein–protein interaction network analysis. In vitro, bronchial epithelial cells treated with cigarette smoke extract (CSE) were used to study the effects on gene expression, cell viability, apoptosis, and ferroptosis. Additionally, Lipocalin 2 (LCN2) inhibition experiments were conducted to elucidate its role in COPD-related cellular processes.ResultsAnalysis of RNA profiles revealed consistent downregulation of 17 genes and upregulation of 21 genes across all COPD groups. Among these, Cathelicidin Antimicrobial Peptide(CAMP), Defensin Alpha 4(DEFA4), Neutrophil Elastase(ELANE), LCN2 and Lactotransferrin(LTF) were identified as potentially important players in COPD pathogenesis. Particularly, LCN2 exhibited a close association with COPD and was found to be involved in cellular processes. In vitro experiments demonstrated that CSE treatment significantly increased LCN2 expression in bronchial epithelial cells in a concentration-dependent manner. Moreover, CSE-induced apoptosis and ferroptosis were observed, along with alterations in cell viability, Glutathione content, Fe2 + accumulation, ROS: Reactive Oxygen Species and Malondialdehyde levels, Lactate Dehydrogenase(LDH) release and Glutathione Peroxidase 4(GPX4) expression. Inhibition of LCN2 expression partially reversed these effects, indicating the pivotal role of LCN2 in COPD-related cellular processes.ConclusionOur study identified six candidate genes: CAMP, DEFA4, ELANE, LCN2, and LTF were upregulated, HSPA1B was downregulated. Notably, LCN2 emerges as a significant biomarker in COPD pathogenesis, exerting its effects by promoting apoptosis and ferroptosis in bronchial epithelial cells.

Effect of Surface-Immobilized States of Antimicrobial Peptides on Their Ability to Disrupt Bacterial Cell Membrane Structure

Antimicrobial peptide (AMP) surfaces are widely used to inhibit biofilm formation and bacterial infection. However, endpoint-immobilized AMPs on surfaces are totally different from free-state AMPs due to the constraints of the surface. In this work, the interactions between AMPs and bacterial cell membranes were analyzed through coarse-grained molecular dynamics and all-atom molecular dynamics simulations. This AMP disrupted membrane structure by altering the thickness and curvature of the membrane. Furthermore, the effect of surface-immobilized states of AMPs on their ability to disrupt membrane structure was revealed. The immobilized AMPs in the freeze-N system could bind to the membrane and disrupt the membrane structure through electrostatic forces between positively charged N-terminal amino acid residues and the negatively charged membrane, while the immobilized AMPs in the freeze-C system were repelled. The results will aid in the rational design of new AMP surfaces with enhanced efficacy and stability.

A Systematic Review of Aquatic Organism Antimicrobial Peptides

Antimicrobial peptides (AMPs), sourced from various organisms, including aquatic life, are promising alternatives to combat antibiotic resistance. Their investigation is essential amid global antibiotic resistance concerns. The invaluable impact of antibiotics on human health, having saved numerous lives, is currently at risk. The growing global incidence of antibiotic-resistant bacteria poses a serious challenge to their ability to effectively treat various illnesses. This situation demands immediate attention and the exploration of alternative medical solutions. One of the most promising alternatives to antibiotics is antimicrobial peptides (AMPs), which can treat bacterial infections, particularly those brought by multi-drug-resistant pathogens. With a particular focus on their antimicrobial properties, this systematic review aims to evaluate and classify recent AMPs isolated from aquatic organisms. This review advances knowledge of these aquatic life-derived AMPs’ potential as alternatives to conventional antibiotics by examining their unique antibacterial characteristics and modes of action. A systematic review of articles published in English between 2014 and 2024 was carried out in the Science Direct, PubMed NCBI and Google Scholar databases using keywords and inclusion and exclusion criteria. A total of 33 potential AMPs isolated from aquatic organisms had been reported, and 21 of the AMPs were reported to have functional antimicrobial activities. Continuous research and study of natural substances, particularly AMPs, remain critical in pursuing alternatives to conventional antibiotics for effective treatments in combating antibiotic resistance. Therefore, ongoing research holds significant importance in identifying and harnessing the potential of AMPs for future medical applications.

NF-κB transcription factors regulate the expression of immunity-related genes in different cell lines of silkworm (Bombyx mori)

The Toll and immune deficiency (IMD) signaling pathways in insects are highly conserved in evolution and regulate the expression of antimicrobial peptides (AMPs) and other immune-related genes mainly through nuclear factor-kappa B (NF-κB) transcription factors. However, the differences of NF-κB transcription factors Rels and Relish in the expression regulation of AMPs and other immune-related genes in silkworm (Bombyx mori) have not been systematically reported. In this study, the BmRelA, BmRelB and BmRelish1 genes were cloned and their eukaryotic cell overexpression vectors were constructed. After the recombinant vectors were transfected into BmE and BmN cells, the expression of AMPs and immune-related genes was detected by real-time fluorescence quantitative PCR. The results showed that the expression of AMP genes Defensin2 and Gloverin2 was mainly regulated by Relish, the expression of Moricin was mainly regulated by RelA and RelB, and the expression of other AMP genes was jointly regulated by both. In addition, the expression levels of peptidoglycan recognition proteins (PGRPs), β-1, 3-glucan recognition proteins (βGRPs), lysozymes (Lys) and lysozyme-like proteins (LLPs), and nitric oxide synthase (NOS) were up-regulated to varying degrees in different cell lines in response to RelA, RelB and Relish1, suggesting that the expression of these immune-molecules was also regulated by Toll or IMD pathways in silkworm. Compared with the regulatory specificity of transcription factors in Drosophila Toll and IMD signaling pathways on the expression of AMPs, this study found that the regulatory patterns of Rels and Relish1 on the expression of AMPs in silkworm are more complex, which provides an experimental basis for further analysis of the effect mechanism and feedback mechanism of Toll and IMD pathways in insects.