Search Results (306)

Rare actinomycetes have emerged as important yet underexplored reservoirs for the discovery of novel bioactive compounds. Microbispora, a genus of rare actinomycetes, is widely distributed across diverse ecological niches, including terrestrial soils, marine-associated environments, plant-associated ecosystems, and insect-derived environments. To date, 81 secondary metabolites have been reported from this genus, encompassing quinones, chromones and chromanones, macrolides, other polyketides, alkaloids, peptides and diketopiperazines, and miscellaneous structural classes. These metabolites display antimicrobial, anticancer, neuroprotective, antiviral, plant growth-promoting, and enzyme inhibitory activities. Beyond systematically cataloging these compounds, this review provides an integrated analysis of their structure–activity relationships (SAR), biosynthetic origins, and biological significance. In addition, the biosynthetic potential of Microbispora is discussed based on reported genomic studies, highlighting the presence of numerous predicted and poorly characterized biosynthetic gene clusters. This review provides an integrative perspective on Microbispora as an underexplored but promising source of structurally diverse and bioactive natural products for drug discovery. Full article

Chagas disease, caused by Trypanosoma cruzi, remains a major public health problem in Latin America and an emerging global health concern due to population mobility. Although benznidazole and nifurtimox remain the only approved antiparasitic drugs, their limited efficacy in chronic infection, prolonged treatment regimens, frequent adverse effects, and variable activity across parasite strains highlight the need for new therapeutic strategies. In addition, the pathogenesis of chronic Chagas disease is driven not only by parasite persistence but also by immune-mediated tissue damage, particularly in chronic Chagas cardiomyopathy. In this review, we examine emerging therapeutic approaches that extend beyond conventional trypanocidal chemotherapy, with emphasis on natural products, antimicrobial peptides, and cell-based immunomodulatory strategies. Plant compounds and essential oils have shown antiparasitic activity through mechanisms including oxidative stress induction, membrane disruption, interference with sterol biosynthesis, and mitochondrial dysfunction, while some extracts also modulate host immune responses. Antimicrobial peptides display dual potential by directly damaging parasite membranes and organelles or by reshaping infection-associated inflammatory responses. In parallel, cell-based therapies such as mesenchymal stromal cells, tolerogenic dendritic cells, and bone marrow-derived cells have demonstrated promising cardioprotective and immunoregulatory effects in experimental chronic Chagas disease. Collectively, these approaches support a multitarget therapeutic framework in which parasite-directed and host-directed interventions may complement each other. Further mechanistic studies, standardization, and translational validation will be essential to advance these candidates toward clinically useful therapies for Chagas disease. Full article

Biofilms are structured communities of microorganisms embedded in a self-produced extracellular polymeric substance (EPS) matrix, whose development significantly enhances microbial resistance to antibiotics, disinfectants, and host immune defenses, posing major challenges in clinical, industrial, and environmental settings. Compared with planktonic cells, biofilm-associated microorganisms can exhibit up to 10- to 1000-fold increased tolerance to antimicrobial agents, contributing to the persistence of biofilm-associated infections (BAIs). These infections remain difficult to eradicate due to reduced penetration, altered metabolic states, and the presence of dormant or persister cells. Anti-biofilm strategies can be broadly classified into physical approaches (e.g., ultrasound, mechanical stress, and light-based approaches) that target biofilm structure; chemical and enzymatic methods (e.g., EPS-degrading enzymes) that destabilize the matrix; and biological and molecular strategies (e.g., quorum-sensing (QS) inhibitors, anti-virulence agents, bacteriophages, phage-derived antimicrobial molecules, antimicrobial peptides, and natural bioactive compounds) that modulate biofilm development and integrity by targeting regulatory pathways and matrix stability through distinct mechanisms of action. Natural compounds, including lactoferrin, lactoferrin-derived peptides, and probiotic and postbiotic fractions of lactic acid bacteria (LAB), as well as plant-derived metabolites, have shown promising anti-biofilm effects, with efficacy often enhanced through complementary or potentially synergistic interactions. However, despite these advancements, clinical translation remains limited. For example, BAIs account for approximately 80% of chronic infections, with high recurrence rates and therapeutic failure reported in device-associated infections and chronic wounds. These limitations highlight the need for clinically translatable, multimodal approaches that integrate structural biofilm disruption, antimicrobial targeting, and host response modulation to design more effective and sustainable anti-biofilm strategies. Full article

Background/Objectives: Cyclotides are plant-derived macrocyclic peptides distinguished by their head-to-tail cyclized backbone and cystine knot motif, which confer remarkable stability against thermal, enzymatic, and chemical degradation. These features, combined with a compact and rigid structure, position cyclotides as promising scaffolds for future antibacterial agents in response to the escalating threat of multidrug-resistant (MDR) pathogens and the stagnation of conventional antibiotic discovery pipelines. This review summarizes the structural features, antibacterial mechanisms, bioengineering strategies, and translational potential of cyclotides against MDR infections. Methods: A narrative review of the literature was conducted using recent original research articles and reviews on cyclotide structure, antibacterial activity, bioengineering, computational modeling, and pharmaceutical applications. Results: Cyclotides exhibit potent antimicrobial activity, primarily through membrane disruption mediated by amphipathic surfaces and affinity for anionic bacterial membranes. Some variants also demonstrate anti-virulence and antibiofilm properties, broadening their therapeutic relevance for difficult-to-treat infections. Bioengineering approaches, including epitope grafting and rational design, have improved selectivity and potency while reducing cytotoxicity. Advances in computational modeling, molecular dynamics, and artificial intelligence have accelerated the prediction and optimization of antimicrobial activity, toxicity, and pharmacokinetic properties. Conclusions: Innovations in synthesis, including recombinant expression and enzymatic ligation, are helping overcome translational barriers related to cost and scalability. Although challenges remain in oral bioavailability and systemic delivery, strategies such as lipidation and scaffold modification support the development of cyclotide-based therapeutics as adaptable platforms for peptide drug discovery. Full article

Cutaneous infections and chronic inflammatory wounds remain difficult to treat because antimicrobial resistance, polymicrobial biofilms, excessive protease activity, oxidative stress, and impaired barrier repair collectively reduce the effectiveness of conventional topical therapies. Plant-derived antimicrobial peptides (AMPs) and peptide-associated bioactives offer antimicrobial, antibiofilm, immunomodulatory, and tissue reparative potential; however, their clinical translation is limited by proteolytic instability, poor stratum corneum penetration, short cutaneous residence time, formulation variability, cytotoxicity risks and limited human evidence. The key research gap is the lack of an integrated translational framework linking plant-derived peptide bioactivity with polymer engineering, advanced delivery systems, skin microenvironment biology, manufacturability, and regulatory feasibility. This review aims to critically evaluate the design principles, therapeutic mechanisms, delivery platforms, and translational barriers of plant-based peptide–polymer therapeutics for cutaneous infection and inflammation. We summarize major classes of plant-derived antimicrobial peptides, including defensins, cyclotides, thionins, hevein-like peptides, snakins, lipid transfer proteins, and knottin-type scaffolds, and examine engineering strategies such as self-assembly, aromatic N-capping, PEGylation, lipidation, dendritic architectures, and stimuli-responsive conjugation. We further discuss topical matrices, nanocarriers, liposomes, electrospun fibers, and surface-tethered biomaterials as delivery platforms for improving peptide stability, local retention, and controlled release. Finally, we identify key translational bottlenecks, including selectivity, toxicity, scalability, batch reproducibility, regulatory classification, and insufficient clinical validation. Mechanism-driven peptide optimization, quality-by-design manufacturing, standardized preclinical models, and controlled clinical trials will be essential for advancing these systems toward safe and effective dermatological therapies. Full article

Background: Nosocomial infections caused by multidrug-resistant microorganisms are a significant public health concern. Antimicrobial resistance (AMR) is closely linked to the excessive and indiscriminate use of antibiotics, which creates selective pressure and promotes the emergence of resistant pathogens. Objectives: This study evaluates the synergistic potential of intragenic antimicrobial peptides (IAPs) combined with plant alkaloids against susceptible and multidrug-resistant human pathogenic bacteria, assessing antimicrobial activity, biofilm inhibition, and hemocompatibility. Methods: The tested molecules included berberine, tomatidine, sinomenine, and the IAPs Hs02 and Gr01. Minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) assays were performed against both ATCC (E. coli ATCC 25922 and S. aureus ATCC 25923) and clinical strains (E. coli KPC+ HRAN 1812446 and S. aureus MDR LACEN 3730529). Synergistic interactions were evaluated by checkerboard assay, followed by biofilm inhibition and hemolysis assays using human red blood cells. Results: Berberine exhibited a MIC of 1024 µM when tested individually, while tomatidine and sinomenine showed no significant activity. As expected, the IAPs showed strong antimicrobial properties at 8 µM (Hs02) and 4 µM (Gr01). When tested in synergy, alkaloids and IAPs reduced the MIC by up to 128-fold. The combination of IAPs and alkaloids reduced the biofilm biomass of S. aureus and E. coli by 50%, by the crystal violet assay (p < 0.05). Notably, sinomenine had not previously been reported to have antimicrobial activity. Conclusions: These results highlight the importance of further exploring combinations of natural and synthetic bioactive molecules as promising antimicrobial candidates. This approach may help to extend the useful life of conventional antibiotics. However, further studies are needed to assess safety, cytotoxicity, genotoxicity, inflammation, and in vivo effects. Full article

The roles of proline in stress tolerance, energy metabolism, immune function, and ecology across organisms suggest a broader relevance in orchard agroecosystems than is often recognized. In fruit trees, stress-induced proline accumulation reflects a complex regulatory network, while evidence also indicates that inter-organ transport contributes to protective responses under abiotic stress. In insects, proline functions as an oxidative substrate priming the rest-to-flight metabolic transition in pollinators and pests, a cryoprotective osmolyte and a structural element of conserved classes of antimicrobial peptides against microbial threats. These roles create paradoxical orchard-scale feedbacks while a stress-protective molecule both intensifies herbivore pressure and enhances pollination and biocontrol services. The orchard environment represents a meeting point of plant, environmental, animal and human health, reflecting the integrative logic of the One Health framework, where proline emerges as a highly water-soluble and bioactive compound. The functional homology between insect and human proline catabolism emerges governance-critical issues across tree physiology, insect immunity and human dietary exposure. The targeted application offers a unifying framework for farmers, scientists and policymakers to advance Sustainable Development Goal commitments across food security, human health, climate resilience and biodiversity. We conclude that proline supplementation in orchards requires regulatory monitoring across ecophysiological and pharmaceutical dimensions. Full article

Antibiotic resistance has become a significant challenge for global health. Exploring novel antimicrobial compounds as alternatives to antibiotics is increasingly prominent in combating resistant pathogens. Antimicrobial peptides (AMPs), produced by various organisms, are considered natural antibiotic candidates that can be used against multidrug-resistant microorganisms. The snakin family of plant-based AMPs is a promising candidate for use in the agriculture, food and pharmaceutical industries due to its antimicrobial activity against both phytopathogenic and clinical species. This review summarizes current AMP databases and the snakin family of plant AMPs deposited in the Universal Protein Resource, UniProt. It also provides knowledge about potential uses of this family in biotechnology. Full article

Fungal and bacterial pathogens significantly impact global crop yields, causing substantial economic losses and food insecurity. While chemical pesticides are effective, their excessive and improper use poses risks to the environment and human health. Antimicrobial peptides (AMPs)—components of innate immunity in plants and animals—are promising candidates for the development of novel, eco-friendly antimicrobials for agriculture and medicine. This study explores the antimicrobial activity of several γ-core peptides derived from defensins of Thinopyrum elongatum, a wild plant species known for its stress resistance. All peptides carried a net positive charge. 3D structural modeling indicated that most peptides adopted an α-helical conformation, with one predicted to form an anti-parallel β-hairpin structure. The conservation of the γ-core peptide sequences across Poaceae defensins was demonstrated, underscoring the importance of these peptide regions in biological functions of defensins. Antimicrobial assays demonstrated that all peptides exhibited broad-spectrum activity, with efficacy depending on the peptide’s amino acid sequence, 3D structure, and the pathogen tested. Notably, the peptide with the highest positive charge and β-hairpin structure showed the strongest pathogen inhibition. Additionally, synergistic interactions between some peptides against Fusarium oxysporum, which enhanced their antimicrobial effects, were shown. Our findings highlight the potential of wheatgrass γ-core peptides as templates for developing new peptide-based antimicrobials for agricultural and medical applications. Full article

Antimicrobial peptides (AMPs) are natural bioactive peptides produced by all organisms—from plants to insects, microbes and animals—and constitute a first line of defense. As they exhibit a broad spectrum of activity (antibacterial, antiviral, antifungal, antiparasitic, anticancer), strong efforts are being made to integrate AMPs into clinical use. AMPs are also being investigated as anticancer agents to overcome the side effects and/or resistance associated with current chemotherapies. In this context, we identified the natural AMP chionodracine from a new biological source: an Antarctic fish. Starting from the fragmentation of a chionodracine mutant peptide, a rational modular design approach was applied to develop three very short peptides (Pep-A, Pep-B and Pep-C), which were further modified with an N-terminal myristic acid lipid tail. The anticancer activity of the three N-myristoylated short peptides (Myr-A, Myr-B and Myr-C) was explored against the human cervical cancer HeLa cell line. The rationale behind this study is based on the previously reported antifungal activity of these myr peptides and on their ability to interact selectively with biological membrane-mimicking synthetic phospholipids without being particularly hemolytic or cytotoxic towards normal cells. We first demonstrated that myr peptides had cytotoxic activity against HeLa cells (IC₅₀ from 32 to 47 μM) but spared healthy primary human fibroblasts, whereas the corresponding non-myr peptides failed to kill cancer cells. The peptide with no hemolytic activity and a low IC₅₀, labeled Myr-B, was selected for subsequent analyses. Lactate dehydrogenase (LDH) assay and scanning electron microscopy (SEM) analysis revealed membrane damage and predominantly necrotic cell death in HeLa cells exposed to IC₅₀ doses of the Myr-B peptide, compared with cells treated with Pep-B. To thoroughly investigate the molecular effects of Myr-B in HeLa cells, we employed high-resolution label-free shotgun quantitative proteomics coupled with bioinformatics. Our results showed that exposing HeLa cells to Myr-B led to the under-expression of proteins belonging to the “apoptosis- and splicing-associated protein complex”, potentially influencing the alternative splicing process and consequently leading to a possible susceptibility to programmed cell death. These findings indicate that modifying natural AMPs may be a promising strategy for developing selective anticancer drugs and pinpoint Myr-B as an interesting target for future studies. Full article

The global wine industry generates approximately 20 million tonnes of organic residues annually, representing a significant environmental and management challenge. While phenolic compounds from winery by-products have been extensively studied, protein and peptide fractions remain underutilised. This review provides a systematic overview of proteins derived from major winery side streams, including grapevine leaves, stems, pomace, seeds, and wine lees, with emphasis on their characterisation and recovery. Conventional and emerging extraction strategies are evaluated, with particular attention to green technologies such as ultrasound-assisted extraction (UAE), pulsed electric fields (PEF), and natural deep eutectic solvents (NADES) in the context of sustainable and resource-efficient processing. Enzymatic hydrolysis is discussed as a key approach for converting complex proteins into bioactive peptides with antioxidant, antimicrobial, and antihypertensive properties. Potential applications in agriculture, plant protection, animal nutrition, and food systems are considered, together with the implications of the EU circular economy regulatory framework. Overall, winery by-products are highlighted as promising nitrogen-rich secondary resources, and the review outlines valorisation pathways supporting nutrient recycling, waste reduction, and the development of a more sustainable agricultural bioeconomy. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) is a major clinical problem due to its resistance, virulence, and biofilm formation, which diminish antibiotic efficacy. This review explores natural products and antimicrobial nanoparticles (NPs) as alternative and combined strategies for controlling MRSA. Natural compounds, such as plant metabolites, essential oils, antimicrobial peptides, and fungal products, act by disrupting membranes, interfering with cellular processes, and limiting biofilm formation. Antimicrobial NPs, especially metal and metal oxide materials, act through membrane damage, oxidative stress, and metal ion release, enabling activity against resistant bacteria and improving biofilm penetration. Combining natural products with NPs increases stability, delivery, and local activity, enhances antibacterial effects, and reduces effective doses. Green synthesis enables direct integration of bioactive compounds, while nano-delivery platforms optimize solubility and controlled release. Nanotechnology-based applications such as wound dressings, nanocarriers, and multifunctional platforms support localized and sustained treatment and promote tissue repair. Despite these advances, clinical use is still constrained by safety concerns, variability in NP properties, and the lack of standardized evaluation and regulatory frameworks. Overall, combining natural products with antimicrobial NPs offers a practical strategy to augment MRSA treatment, but further progress depends on consistent design, robust safety evaluation, and clinical translation. Full article

The identification of novel natural sources of bioactive peptides with multifunctional health-promoting properties remains a major challenge for the development of nutraceutical and therapeutic agents. Prosopis laevigata (mesquite), a plant of economic, medicinal, and nutritional relevance in Mexico, has been poorly explored as a source of protein-derived bioactive molecules. Therefore, this study evaluated the antioxidant, antimicrobial, cytotoxic, and enzymatic inhibitory activities of peptides obtained from the enzymatic hydrolysis of P. laevigata cotyledon proteins. The resulting hydrolysates exhibited significant antioxidant activity, for peptide fractions smaller and larger than 5 kDa, in the ABTS and FRAP assays. Cytotoxic activity against HepG2 liver cancer cells was observed at high peptide concentrations (8 mg/mL). Additionally, the peptides inhibited the growth of Staphylococcus aureus but showed no activity against Escherichia coli. The peptides also displayed partial inhibition of α-amylase activity, with peptides <5 kDa exhibiting competitive inhibition and peptides >5 kDa showing a mixed inhibition pattern. Overall, these findings highlight P. laevigata seeds as a promising source of multifunctional bioactive peptides with potential applications in functional foods and health-related biotechnological developments. Full article

Xanthomonas campestris pv. campestris (Xcc) is the causal agent of black rot, one of the most destructive bacterial diseases on crucifer crops, resulting in yield losses of up to 90%. The aim of this study was to identify novel endophytic bacteria from cabbages with potential biocontrol agents against Xcc. A total of sixty-five isolates were evaluated for plant growth-promoting characters and antagonistic activity, from which ten were selected for in planta assays and subsequently validated under field conditions. Pseudomonas synxantha BR25/2 consistently demonstrated the highest efficacy, reducing disease severity by 81.12% in in planta trials and 33.5% in field trials, thereby comparing to copper-based control measures. Additionally, Pseudomonas synxantha BR25/2 significantly enhanced yield parameters, including a 31.8% increase in head weight under field conditions. Whole-genome sequencing identified biosynthetic gene clusters, including siderophores, phenazines, and non-ribosomal peptide synthetases, notably a coronatine-like NRPS and a fengycin-like betalactone, suggesting an extensive antimicrobial potential of metabolites. This represents the first report of P. synxantha exhibiting control over Xcc. For commercial application, large-scale fermentation and encapsulation techniques are recommended to overcome shelf-life challenges, providing a sustainable microbial solution for crucifer production. Full article

Canker and dieback diseases caused by fungal pathogens represent an increasing threat to woody plants in both urban and forest environments, where sustainable management options are urgently needed. In this study, the biocontrol potential of Bacillus strain N1 was investigated against Neofusicoccum parvum and Gnomoniopsis smithogilvyi, causal agents of canker diseases on Eucalyptus globulus and Castanea sativa, respectively. The whole-genome sequence confirmed the taxonomic identification of strain N1 as B. velezensis, showing high average nucleotide identity and digital DNA–DNA hybridization values with reference strains. AntiSMASH analysis revealed the presence of multiple biosynthetic gene clusters associated with the production of antimicrobial secondary metabolites, including polyketides, non-ribosomal peptides, and lipopeptides, reflecting strain N1’s genomic potential to produce compounds that may contribute to its antifungal activity. Moreover, B. velezensis strain N1 significantly inhibited the growth of N. parvum and G. smithogilvyi and showed a biocontrol efficacy on detached eucalyptus and chestnut shoots. In both preventive and curative treatments and pathosystems, the application of B. velezensis N1 resulted in a significant reduction in the length of necrotic lesions, compared to pathogen-only controls, while no phytotoxic effects were observed on treated shoots. Overall, this study supported B. velezensis N1 as a promising candidate for the sustainable control of canker-associated pathogens in woody plants. Full article