Search Results (216)

The synthesis of biocidal peptide materials using simple, low-cost, solvent-free methods is a crucial challenge for developing new antimicrobial approaches. In this study, we produced proteinoid nanostructures through simple, inexpensive, and environmentally friendly thermal reactions between glutamic acid (Glu) and tyrosine (Tyr) in various molar ratios. Mechanistically, the thermal cyclization of glutamic acid into pyroglutamic acid (pGlu) facilitated the formation of short peptide chains containing pGlu as the N-terminus moiety and subsequent L-tyrosine or glutamic acid residues, which self-assembled into nanometric spheroidal structures that exhibit blue emission. Spectroscopic (FTIR, UV-Vis, photoluminescence) and mass (LC-MS) analyses confirmed the formation of mixed pGlu-/Tyr/Glu peptides. All products exhibit dose-dependent antimicrobial activity against Methicillin-Resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 25 mg mL⁻¹ for the GluTyr 1:1 and 2:1 proteinoids. The outcomes observed following 24 h exposure of the HEK293 cell line to the materials indicate their suitability for integration into hybrid systems for antimicrobial surfaces. This work is the first to demonstrate a direct antibacterial activity of proteinoids obtained by thermal condensation, opening up the possibility of designing a new class of synthetic antimicrobial peptides. Full article

Background: Pruritus is burdensome across dermatoses. Beyond Staphylococcus, broader components of the cutaneous microbiome—bacteria, fungi, and viruses—and their products shape itch via barrier disruption, immune polarization, and direct neurosensory activation. Methods: We conducted a narrative review of human and translational studies. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to 27 August 2025 using terms for itch, skin microbiome, bacteriotherapy, proteases, PAR, TRP channels, IL-31, Malassezia, and AHR ligands. English and Italian records were screened; randomized trials, systematic reviews, and mechanistic studies were prioritized; and unsupported single case reports were excluded. Results: Beyond Staphylococcus aureus, microbial drivers include secreted proteases activating PAR-2/4; pore-forming peptides and toxins engaging MRGPRs and sensitizing TRPV1/TRPA1; and metabolites, especially tryptophan-derived AHR ligands, that recalibrate barrier and neuro-immune circuits. Commensal taxa can restore epidermal lipids, tight junctions, and antimicrobial peptides. Early studies of topical live biotherapeutics—Roseomonas mucosa and Staphylococcus hominis A9—report reductions in disease severity and itch. Fungal communities, particularly Malassezia, contribute via lipases and bioactive metabolites with context-dependent effects. Across studies, heterogeneous itch metrics, small samples, and short follow-up limit certainty. Conclusions: The cutaneous microbiome actively contributes to itch and is targetable. Future studies should prioritize standardized itch endpoints, responder stratification, and robust safety for live biotherapeutics. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with immune dysregulation, skin barrier dysfunction, and microbial dysbiosis characterized by Staphylococcus aureus overcolonization and reduced bacterial diversity. Beyond its classical role in calcium homeostasis, Vitamin D (VD) influences skin immunity and microbial composition. This review summarizes current knowledge on VD metabolism, its immunological pathways in AD, and its interactions with the skin microbiome. Recent evidence positions the skin as an active immunological organ rather than a passive barrier. Commensal bacteria such as Staphylococcus epidermidis not only inhibit pathogens by producing bacteriocins and modulins but also generate ceramides and short-chain fatty acids (SCFAs) that stabilize the lipid barrier. Moreover, dermal fibroblasts and preadipocytes produce antimicrobial peptides, while resident γδ T cells release growth factors like fibroblast growth factor 7 (FGF7), linking host defense with tissue regeneration. VD modulates AD by suppressing T helper 2 cells/T helper 17 cell responses, enhancing regulatory T cell development, inducing antimicrobial peptides, and strengthening skin and gut barrier integrity. Its interaction with the microbiome and pathways such as SCFA and aryl hydrocarbon receptor (AhR) signaling supports its potential as an adjunctive therapy in AD management. Evidence from mechanistic studies and animal models suggests that VD supplementation may modulate inflammation and microbial diversity. Clinical implications, therapeutic perspectives, and future research directions highlight the potential of VD as a therapeutic adjunct in AD management. Full article

Pulses and pseudocereals are sustainable protein sources of bioactive peptides (BAPs) with potential antioxidant, antihypertensive, antidiabetic, antimicrobial, and immunomodulatory activities. BAPs are typically liberated during gastrointestinal digestion or through bio-based processes, among which enzymatic hydrolysis and microbial fermentation represent the most widely applied strategies. Enzymatic hydrolysis provides controlled and reproducible release of short peptide motifs; recent advances such as ultrasound- or high-pressure–assisted hydrolysis enhance yield and bioactivity. Fermentation exploits microbial proteolytic activity to generate complex peptide mixtures, while improving sensory quality, reducing antinutritional compounds, and responding to consumer demand for natural and “clean-label” products. In silico tools increasingly complement these approaches by accelerating peptide discovery, predicting interactions with molecular targets, and guiding process design. This review provides an updated overview of bio-based methods to produce BAPs from pulses and pseudocereals, emphasizing the comparative advantages of enzymatic and fermentation technologies and their integration with computational tools. Moreover, it examines regulatory frameworks in the European Union, the United States, Japan, and China, while discussing current challenges for industrial scale-up and application in functional foods and nutraceuticals. These combined strategies offer a promising pathway to unlock the health and sustainability potential of plant proteins. Full article

In this study, we successfully cloned the fluorescent proteins eGFP and DsRed in-frame with the antimicrobial peptide epinecidin-1 (FIFHIIKGLFHAGKMIHGLV) at the N-terminal. The cloning strategy involved inserting the fluorescent reporters into the expression vector, followed by screening for positive clones through visual fluorescence detection and molecular validation. The visually identified fluorescent colonies were confirmed as positive by PCR and plasmid migration assays, indicating successful cloning. This fusion of fluorescent reporters with a short antimicrobial peptide enables real-time visualization and monitoring of the peptide’s mechanism of action on membranes and within cells, both in vivo and in vitro. The fusion of eGFP and DsRed to epinecidin-1 did not impair the expression or fluorescence of the reporter protein. Full article

The growing prevalence of antimicrobial resistance has significantly compromised the efficacy of conventional antibiotic-based interventions in controlling Salmonella infections across human and veterinary settings. This growing challenge necessitates a strategic rethinking of pathogen control, prompting the integration of next-generation therapeutics capable of disrupting Salmonella pathogenesis through novel, antibiotic-sparing mechanisms. In this context, a diverse array of emerging alternatives, including bacteriophages, antimicrobial peptides, probiotics, prebiotics, short-chain fatty acids, nanoparticles, and host-directed immunomodulators, have gained prominence as a promising frontier in non-antibiotic therapeutics. These modalities offer targeted approaches to inhibit Salmonella colonization, virulence expression, and persistence, while minimizing collateral damage to the microbiota and avoiding the propagation of resistance genes. As Salmonella continues to pose a global threat to animal and public health, the development of scalable, resistance-conscious interventions remains a critical priority. Ongoing research efforts are increasingly focused on optimizing delivery systems, dosage strategies, and synergistic combinations to enhance the clinical and field applicability of these alternatives. By harnessing these innovative modalities, the future of Salmonella control may shift toward precision therapeutics that align with One Health principles and sustainable food safety goals. Full article

The increase in antibiotic-resistant pathogens has prompted the search for alternative therapies. One such alternative is the use of probiotic microorganisms. However, growing interest is now turning toward postbiotics—non-viable microbial cells and/or their components or metabolites—that can confer health benefits without the risks associated with administering live microbes. Marine ecosystems, characterized by extreme and diverse environmental conditions, are a promising yet underexplored source of microorganisms capable of producing unique postbiotic compounds. These include bioactive peptides, polysaccharides, lipoteichoic acids, and short-chain fatty acids produced by marine bacteria. Such compounds often exhibit enhanced stability and potent biological activity, offering therapeutic potential across a wide range of applications. This review explores the current knowledge on postbiotics of marine origin, highlighting their antimicrobial, anti-inflammatory, immunomodulatory, and anticancer properties. We also examine recent in vitro and in vivo studies that demonstrate their efficacy in human and animal health. Some marine bacteria that have been studied for use as postbiotics belong to the genera Bacillus, Halobacillus, Halomonas, Mameliella, Shewanella, Streptomyces, Pseudoalteromonas, Ruegeria, Vibrio, and Weissella. In conclusion, although the use of the marine environment as a source of postbiotics is currently limited compared to other environments, studies conducted to date demonstrate its potential. Full article

Bioactive peptides encrypted in bovine β-casein display diverse physiological functions, including antihypertensive, antioxidative, antimicrobial, and immunomodulatory activities. These peptides are normally released during gastrointestinal digestion or microbial fermentation, especially by proteolytic systems of lactic acid bacteria (LAB). However, peptide yields vary widely among LAB strains, reflecting strain-specific protease repertoires. To overcome these limitations, the scientific goal of this study is to provide a comprehensive synthesis of how synthetic biology, molecular biotechnology, and systems-level approaches can be leveraged to enhance the targeted discovery and production of β-casein-derived bioactive peptides. Genome engineering tools such as clustered regularly interspaced short palindromic repeats associated system (CRISPR/Cas) systems have been applied to modulate gene expression and metabolic flux in LAB, while inducible expression platforms allow on-demand peptide production. Additionally, cell-free systems based on LAB lysates further provide rapid prototyping for high-throughput screening. Finally, multi-omics approaches, including genomics, transcriptomics, proteomics, and metabolomics, further help pinpoint regulatory bottlenecks and facilitate rational strain optimization. This review provides a comprehensive overview of bioactive peptides derived from bovine β-casein and highlights recent progress in LAB-based strategies—both natural and engineered—for their efficient release. These advances pave the way for developing next-generation functional fermented foods enriched with targeted bioactivities. Full article

Antimicrobial peptides (AMPs) are the promising candidates for the development of next-generation antimicrobials for agriculture and medicine; however, their large-scale production is costly. The γ-core motif peptides, functionally significant fragments of AMPs responsible for the antimicrobial activity, provide a more economical and feasible approach for the commercial development of novel antimicrobials. In the present work, we undertook a comprehensive study of antimicrobial properties of several γ-core peptides derived from defensins and snakins of Filipendula ulmaria, a medicinal plant known for its valuable pharmacological properties. The γ-core peptides were produced by solid-phase synthesis and purified by RP-HPLC. Their physicochemical properties underlying biological activity were predicted. All the peptides ranging in size from 14 to 18 amino acid residues were positively charged. All peptides except one were predicted to be α-helical and antimicrobial. The synthetic peptides were in vitro tested against a wide panel of plant and human fungal and bacterial pathogens. A short overview of the pathogens used in antimicrobial assays with a special emphasis on their economic, social, and medicinal impacts is provided. As a result of our work, we identified the peptides with pronounced activity in low-micromolar range against particular pathogens that can serve as prototypes for the development of novel biopesticides and antimicrobials for medicine. We also revealed synergism of action between particular γ-core peptide pairs and demonstrated that interference with membrane permeabilization contributes to the peptides’ mode of action. The results obtained broaden our understanding of plant AMPs, the key players in plant immunity, and provide novel highly efficient peptides with high potential in practical applications. Full article

The rise of multidrug-resistant pathogens has become a serious health concern, creating an urgent need for novel therapeutic approaches. Among the compounds explored, AMPs have emerged as promising candidates due to their broad-spectrum activity and low propensity for resistance development. However, their clinical implementation is limited by improper size, in vivo instability, and toxicity. Here, we designed short analogs of CeHS-1 via (1) truncation of intact CeHS-1, (2) amino acid substitution, (3) end-tagging, and (4) C-terminal amidation. The results showed that short analogs fused with an RWW stretch exhibited stronger antibacterial activity than the parent analogs, without inducing hemolysis in human red blood cells. Among the tested AMPs, mechanistic studies revealed membrane-disruptive activity of certain peptides against Staphylococcus aureus. In silico analyses also suggested that the analogs bind DNA by aligning parallel to its grooves, where the RWW stretch is believed to contribute to interactions between arginine and tryptophan residues and nitrogenous bases through electrostatic, hydrogen bonding, and hydrophobic interactions. The short CeHS-1 analogs established here may serve as potential alternative antimicrobial agents, which should be tested in clinical trials in the future. Full article

Background/Objectives: Burn wound infections present significant clinical challenges due to multidrug-resistant pathogens and the limitations of traditional antimicrobials. While antimicrobial peptides (AMPs) have broad-spectrum effectiveness, their instability in wound environments limits their use. This study compares properties of AMP-decorated nanostructured lipid carriers (NLCs) to free AMPs, focusing on their dermal penetration, retention, and antimicrobial efficacy in simulated ex vivo burn wound models. Methods: AMP-decorated NLCs (smart-AMPs) were produced by electrostatic and hydrophobic surface adsorption and characterized regarding their size, zeta potential, and physical short-term stability. The distribution of AMPs within the wounds was evaluated using an ex vivo porcine ear model with various wound types. The antimicrobial efficacy was assessed by monitoring the bioluminescence of Aliivibrio fischeri as a live bacterial marker for 24 h. Results: The size and zeta potential measurements confirmed the successful formation of smart-AMPs. The dermal penetration of AMPs was influenced by the type of wound and the type of AMP formulation (free AMPs vs. smart-AMPs). In the chronically infected burn wounds, which were characterized by the formation of a biofilm in a protein-rich wound fluid, the smart-AMPs resulted in a 1.5-fold higher and deeper penetration of the AMPs, and the antimicrobial activity was 6-fold higher compared to the free AMPs. Conclusions: smart-AMPs present an innovative approach for treating chronic, biofilm-associated wounds more efficiently than the current treatment options. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Probiotic supplementation in domestic cats has emerged as a promising non-pharmaceutical strategy to enhance gut health, immune function, and overall well-being. This review critically examines the current literature on probiotic use in feline health, highlighting evidence from studies involving both healthy and diseased cats. Probiotic strains such as Lactobacillus, Bifidobacterium, Bacillus, Enterococcus, and Saccharomyces have demonstrated beneficial effects, including the modulation of the gut microbiota, a reduction in inflammation, and an improvement in gastrointestinal symptoms. Mechanistically, probiotics exert effects through microbial competition, the enhancement of epithelial barrier function, and immune modulation via cytokine and antimicrobial peptide regulation. Despite promising outcomes, limitations such as short study durations, small sample sizes, and narrow breed diversity constrain generalizability. Future research should prioritize long-term, multi-omics-integrated studies to elucidate mechanisms and optimize clinical application. Overall, probiotics offer a safe, functional dietary tool for improving feline health and may complement conventional veterinary care. Full article

Antimicrobial resistance (AMR) has emerged as one of the most pressing global health challenges of our time. Alarming projections of increasing mortality from resistant infections highlight the urgent need for innovative solutions. While many candidates have shown promise in preliminary studies, they often encounter challenges in terms of efficacy and safety during clinical translation. This review examines cutting-edge approaches to combat AMR, with a focus on engineered antimicrobial peptides, functionalized nanoparticles, and advanced genomic therapies, including Clustered Regularly Interspaced Short Palindromic Repeats-associated proteins (CRISPR-Cas systems) and phage therapy. Recent advancements in these fields are critically analyzed, with a focus on their mechanisms of action, therapeutic potential, and current limitations. Emphasis is given to strategies targeting biofilm disruption and quorum sensing interference, which address key mechanisms of resistance. By synthesizing current knowledge, this work provides researchers with a comprehensive framework for developing next-generation antimicrobials, highlighting the most promising approaches for overcoming AMR through rational drug design and targeted therapies. Ultimately, this review aims to bridge the gap between experimental innovation and clinical application, providing valuable insights for developing effective and resistance-proof antimicrobial agents. Full article

Opioids are among the most effective drugs for treating moderate to severe pain. Unfortunately, opioid use, even short-term, can lead to addiction, tolerance, overdose, and respiratory depression. Therefore, efforts to design and develop novel compounds that would retain analgesic activity while reducing side effects continue unabated. The present study was designed to investigate the respiratory and cardiovascular effects of the hybrid peptide LENART01, which has evidenced potent antinociceptive and antimicrobial activity. This hybrid peptide, composed of N-terminally located dermorphin and C-terminal modified ranatensin pharmacophore, was tested in vivo in anesthetized rats. The main effect of LENART01 was apnea in 70% of examined animals, sighing, and a significant increase in blood pressure. Interestingly, the hybrid induced sighs less frequently than ranatensin, and apnea dependent on vagus nerve mu opioid receptor activation much less frequently and less intensely than dermorphin itself. This shows that LENART01 is a safer opioid system-related agent as compared to dermorphin for its prospective use in the treatment of pain. Full article