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Several microbiome studies have recently demonstrated microbial dysbiosis in various chronic inflammatory skin diseases, and it is considered an important role in the pathogenesis. Although the role of skin dysbiosis in inflammatory skin diseases is debatable, the local microenvironment is considered essential concerning compositional changes and functional alterations of the skin microbiota. Indeed, various local nutrients (e.g., lipids), pH values, water, oxygen, and antimicrobial peptides may affect the level of skin dysbiosis in these skin diseases. In particular, in atopic dermatitis and hidradenitis suppurativa, significant changes in skin dysbiosis have been associated with local aberrant host immune changes. In this review, the potential pathogenic crosstalk between the host and the microbiota is reviewed in relation to the physical, chemical, and biological microenvironments of various chronic inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

Aging is associated with a decline in oral immune function, marked by reduced levels of antimicrobial peptides such as defensins. Capsaicin, a bioactive component found in chili peppers, has been theorized to modulate immune responses through specific receptor pathways. This study examined the effects of aging on oral defensin levels and the potential mitigating role of capsaicin, mediated by the immune response in oral tissues. We conducted a comparative analysis between young and aged mice, with or without capsaicin supplementation, for 3 months. The effect of capsaicin was also studied in vitro in senescence‐induced human oral keratinocytes. We found that aging did not reduce defensin levels uniformly but did so in some instances. Capsaicin treatment increased defensin levels in these cases, potentially through transient receptor potential cation channel subfamily V member 1 (TRPV1)‐mediated pathways in the oral cavity. Capsaicin supplementation may counteract age‐related declines in oral defensin levels, enabling the maintenance of oral immune function during aging. [ABSTRACT FROM AUTHOR]

Summary Plants offer a promising chassis for the large‐scale, cost‐effective production of diverse therapeutics, including antimicrobial peptides (AMPs). However, key advances will reduce production costs, including simplifying the downstream processing and purification steps. Here, using Nicotiana benthamiana plants, we present an improved modular design that enables AMPs to be secreted via the endomembrane system and sequestered in an extracellular compartment, the apoplast. Additionally, we translationally fused an AMP to a mutated small ubiquitin‐like modifier sequence, thereby enhancing peptide yield and solubilizing the peptide with minimal aggregation and reduced occurrence of necrotic lesions in the plant. This strategy resulted in substantial peptide accumulation, reaching around 2.9 mg AMP per 20 g fresh weight of leaf tissue. Furthermore, the purified AMP demonstrated low collateral toxicity in primary human skin cells, killed pathogenic bacteria by permeabilizing the membrane and exhibited anti‐infective efficacy in a preclinical mouse (Mus musculus) model system, reducing bacterial loads by up to three orders of magnitude. A base‐case techno‐economic analysis demonstrated the economic advantages and scalability of our plant‐based platform. We envision that our work can establish plants as efficient bioreactors for producing preclinical‐grade AMPs at a commercial scale, with the potential for clinical applications. [ABSTRACT FROM AUTHOR]

Aim: To investigate the dynamic recovery of biofilms within dentinal tubules after primary irrigation with different protocols, and to evaluate the efficacy of various re‐irrigation protocols on recovered biofilm, considering factors such as smear layer, nutrient conditions, and primary irrigants. Methodology: A total of 416 mono or multi‐species biofilms samples were prepared from human teeth and incubated for 3 weeks. After inducing a smear layer on half of the samples, all specimens were irrigated with one of the following irrigant sequences: (1) 6% NaOCl +17% EDTA, (2) 6% NaOCl +8.5% EDTA, (3) 6% NaOCl and (8.5% EDTA +10 μg/mL DJK‐5 antimicrobial peptide), or (4) sterile water. Thirty‐two samples were used to assess immediate effect, whilst the rest were re‐incubated to assess biofilms recovery. Nutrient conditions were defined based on whether culture media were changed (nutrient‐rich) or not (nutrient‐poor) during re‐incubation. After 16 weeks, recovered biofilms underwent re‐irrigation using four additional protocols, with or without DJK‐5 peptide, based on primary irrigants. Confocal laser scanning microscopy was employed to evaluate immediate irrigant effects, biofilms recovery intervals (1, 3, 5, 8, 12, and 16 weeks after primary irrigation), and re‐irrigation effects at the 16‐week. Statistical analysis included one‐way anova and two‐way mixed anova tests. Results: The DJK‐5 peptide irrigation protocols demonstrated the highest killing rates during primary irrigation and resulted in a longer biofilms recovery time of 16 weeks compared to non‐peptide protocols (p <.001). Both primary irrigation type and smear layer presence significantly influenced biofilms recovery (p <.001). In the absence of smear layer, re‐irrigation efficacy didn't significantly differ from primary irrigation, regardless of primary irrigation type or nutrient conditions. However, with a smear layer present, re‐irrigation led to significantly higher proportion of dead bacteria compared to primary irrigation (p <.05). Inclusion of the DJK‐5 peptide into the re‐irrigation protocol displayed superior killing rate compared to other protocols (p <.001). Conclusions: Biofilms exhibited susceptibility to both peptide and non‐peptide protocols during re‐irrigation, irrespective of nutrient conditions or primary irrigation protocols. The DJK‐5 peptide irrigation protocols consistently displayed superior effectiveness compared to non‐peptide protocols. [ABSTRACT FROM AUTHOR]

Aim: To test the hypothesis that liver‐expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity. Methods: Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin‐like growth factor‐1 (IGF‐1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex‐stratified analyses were also conducted. Results: Five SNPs showed positive associations with obesity‐related traits. rs57880964 was associated with body mass index (BMI) and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF‐1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF‐1 concentration in both sexes. Conclusions: These findings reveal sex‐specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF‐1 concentration. [ABSTRACT FROM AUTHOR]

Gut microbial communities confer protection against natural pathogens in important pollinators from the genera Bombus and Apis. In commercial species B. terrestris and B. impatiens, the microbiota increases their resistance to the common and virulent trypanosomatid parasite Crithidia bombi. However, the mechanisms by which gut microorganisms protect the host are still unknown. Here, we test two hypotheses: microbiota protect the host (1) through stimulation of its immune response or protection of the gut epithelium and (2) by competing for resources with the parasite inside the gut. To test them, we reduced the microbiota of workers and then rescued the microbial community by feeding them with microbiota supplements. We then exposed them to an infectious dose of C. bombi and characterised gene expression and gut microbiota composition. We examined the expression of three antimicrobial peptide genes and Mucin‐5AC, a gene with a putative role in gut epithelium protection, using qPCR. Although a protective effect against C. bombi was observed in bumblebees with supplemented microbiota, we did not observe an effect of the microbiota on gene expression that could explain alone the protective effect observed. On the other hand, we found an increased relative abundance of Lactobacillus bacteria within the gut of infected workers and a negative correlation of this genus with Gilliamella and Snodgrassella genera. Therefore, our results point to a displacement of bumblebee endosymbionts by C. bombi that might be caused by competition for space and nutrients between the parasite and the microbiota within the gut. [ABSTRACT FROM AUTHOR]

Plant disease control faces a lot of challenges due to its overdependence on chemicals that have strict restrictions and regulatory requirements. With the increase in drug‐resistant pathogens and continual crop losses due to disease outbreaks, much attention has been brought to a new set of emerging antibiotics called antimicrobial peptides (AMPs). AMPs are a group of multifunctional, short‐sequence peptides that are usually cationic in nature and found in all living organisms. They are part of the innate immune system of different organisms and exhibit a wide range of inhibitory effects on microorganisms, making them potential therapeutic factors efficacious as an alternate resource for plant disease management. AMPs interact with the anionic cell membrane of the pathogen and cause cell lysis or inhibit crucial intracellular targets. AMPs can be isolated from almost all life forms ranging from microbes to mammals. In addition to these sources, AMPs are also being synthesized using recombinant methods with the goal of overcoming the constraints of natural AMPs with regard to stability, activity and toxicity. Recent advancements have been made to develop transgenic plants expressing AMPs that has proved to perform better than the use of antibiotics. This review highlights the different kinds of AMPs produced by plants and microorganisms along with their mode of action, target pathogens, structural characteristics and advancements in this field, which include isolation methods, synthetic AMPs and transgenic plants expressing AMPs. [ABSTRACT FROM AUTHOR]

Agricultural crops are targeted by various pathogens (fungi, bacteria, and viruses) and pests (herbivorous arthropods). Antimicrobial and insecticidal peptides are increasingly recognized as eco‐friendly tools for crop protection due to their low propensity for resistance development and the fact that they are fully biodegradable. However, historical challenges have hindered their development, including poor stability, limited availability, reproducibility issues, high production costs, and unwanted toxicity. Toxicity is a primary concern because crop‐protective peptides interact with various organisms of environmental and economic significance. This review focuses on the potential of genetically encoded peptide libraries like the use of two‐hybrid‐based methods for antimicrobial peptides identification and insecticidal spider venom peptides as two main approaches for targeting plant pathogens and pests. We discuss some key findings and challenges regarding the practical application of each strategy. We conclude that genetically encoded peptide library‐ and spider venom‐derived crop protective peptides offer a sustainable and environmentally responsible approach for addressing modern crop protection needs in the agricultural sector. [ABSTRACT FROM AUTHOR]

Insects are known to dominate adverse ecological conditions due to their diverse adaptations and resilient biological traits, with their immune systems playing a crucial role in this dominance. Traditionally, insects were thought to lack adaptive immune responses due to their inability to produce antibodies and transfer immunity across generations. However, recent research using insects as model organisms has challenged this notion, revealing that prior exposure to sublethal doses of pathogens or pathogen‐derived materials can protect against subsequent lethal exposures—a phenomenon known as ‘immune priming’. Evidence of bacterial, fungal and viral immune priming across different insect species highlights various types of priming, including trans‐stadial (across life stages) and trans‐generational (across generations) priming. Despite differing views on immune priming, its potential applications in agriculture are considerable, especially in biological control, the utilization of beneficial insects and sustainable pest management. This review explores the intricate dynamics of immune priming in insects, comparing it to vertebrate immunity and investigates its mechanisms, potential agricultural applications and future prospects. [ABSTRACT FROM AUTHOR]

Hydrogels with cell adhesive moieties stand out as promising materials to enhance tissue healing and regeneration. Nonetheless, bacterial infections of the implants represent an unmet major concern. In the present work, we developed an alginate hydrogel modified with a multifunctional peptide containing the RGD cell adhesive motif in combination with an antibacterial peptide derived from the 1–11 region of lactoferrin (LF). The RGD‐LF branched peptide was successfully anchored to the alginate backbone by carbodiimide chemistry, as demonstrated by 1H NMR and fluorescence measurements. The functionalized hydrogel presented desirable physicochemical properties (porosity, swelling and rheological behavior) to develop biomaterials for tissue engineering. The viability of mesenchymal stem cells (MSCs) on the peptide‐functionalized hydrogels was excellent, with values higher than 85 % at day 1, and higher than 95 % after 14 days in culture. Moreover, the biological characterization demonstrated the ability of the hydrogels to significantly enhance ALP activity of MSCs as well as to decrease bacterial colonization of both Gram‐positive and Gram‐negative models. Such results prove the potential of the functionalized hydrogels as novel biomaterials for tissue engineering, simultaneously displaying cell adhesive activity and the capacity to prevent bacterial contamination, a dual bioactivity commonly not found for these types of hydrogels. [ABSTRACT FROM AUTHOR]

The present work demonstrates the effective synthesis of amide derivatives of Nα‐protected amino acids and aryl/heteroaryl amines using di‐2‐pyridyl carbonate (2‐DPC) and cat. DMAP mediated coupling reaction. Several coupling methods were employed for the screening of the amides using EDC, HATU, mixed anhydride, T3P, CDI, COMU, DPTC, and 2‐DPC, where 2‐DPC/cat. DMAP method furnished amides with better yields and purity in shorter durations. Seventeen amide derivatives (3 a–3 q) were successfully synthesized using the present protocol and were characterized by NMR, mass and IR spectroscopy. Further, we performed the in‐silico and in‐vitro studies on the synthesized molecules on antifungal and antibacterial activity. Molecular docking studies reveal the binding affinity of protein‐ligand interactions ranging from −6.2 to −11.0 kcal/mol (Aspergillus Niger Esta), −5.9 to −9.9 kcal/mol (DNA gyrase subunit B) and −6.4 to −13.4 kcal/mol (CYP51B). Compounds like 3 d, 3 e, 3 h, 3 i, 3 j and 3 l exhibit the highest antibacterial and antifungal activity when compared to the standards delafloxacin, ketoconazole, and bifonazole in in‐silico studies. Whereas the in‐vitro studies also unveiled good antimicrobial activity with peptide conjugates. The results of antimicrobial activity exhibits in antifungal species show the good activity concentrations in compounds 3 j is 11.2±3.54 μg/mL and 3 l is 10.3±2.76 μg/mL. The anti‐bacterial species exhibit the compound 3 g showing good activity in different concentrations 12±3.08 μg/mL, 12.2±3.04 μg/mL, 12.6±2.78 μg/mL and 12.5±2.98 μg/mL. [ABSTRACT FROM AUTHOR]

This study utilized molecular dynamics simulations (MD) to explore the impact of cyclization and lysine charges on antimicrobial peptides (AMPs) across eight simulation boxes designed with water and water‐sodium dodecyl sulfate (SDS) micelles. Cyclic AMPs with positively charged lysine residues (c‐AMP+) displayed increased stability in both environments compared to linear AMPs (l‐AMP+), with removal of positive charges notably destabilizing the linear form in water‐SDS. Findings revealed enhanced mobility due to cyclization and charged lysine residues, further boosted by SDS presence. Notably, lysine residues exhibited a stronger affinity for SDS than tryptophan and phenylalanine, especially lysine number 5. Analysis extended to peptide backbone conformation and electronic features, showing cyclization's greater impact on psi and phi angles over charge presence, with linear AMPs displaying lower reactivity than cyclic counterparts. This research underscores the significance of cyclization and lysine charges in AMP behavior, suggesting the potential of c‐AMP+ for further development owing to their improved stability, mobility, and membrane interactions. [ABSTRACT FROM AUTHOR]

This article examines the diverse conjugation forms of AMP‐AuNP nanostructures that arise from the amalgamation of antimicrobial peptides (AMPs) and gold nanoparticles (AuNPs), as well as their prospective utility in the field of biomedicine. AMPs are a class of naturally occurring microbicidal compounds that are recognized for their wide range of inhibitory effects and distinctive modes of operation. The utilization of AuNPs in diverse biomedical applications is facilitated through the application of nanotechnology. AMP‐AuNP nanostructures exhibit diverse features through the utilization of molecular linkage techniques. The aforementioned qualities encompass the ability to expedite the process of wound healing, facilitate precise targeting through the incorporation of DNA aptamers, serve as a means for bacterial imaging, enable the use of photothermal therapy, and contribute to the advancement of prospective treatments for fungal infections. The utilization of these synthesized antimicrobial gold nanostructures in many biomedical applications holds significant promise for advancing treatments and enhancing disease management. [ABSTRACT FROM AUTHOR]

Disease tolerance is an infection phenotype where hosts show relatively high health despite harbouring elevated pathogen loads. Variation in the ability to reduce immunopathology may explain why some hosts can tolerate higher pathogen burdens with reduced pathology. Negative immune regulation would therefore appear to be a clear candidate for a mechanism underlying disease tolerance. Here, we examined how the negative regulation of the immune deficiency (IMD) pathway affects disease tolerance in Drosophila melanogaster when infected with four doses of the gram‐negative bacterial pathogen Pseudomonas entomophila. We find that while flies unable to regulate the IMD response exhibited higher expression of antimicrobial peptides and lower bacterial loads as expected, this was not accompanied by a proportional reduction in mortality. Instead, ubiquitous UAS‐RNAi knockdown of negative regulators of IMD (pirk and caudal) substantially increased the per‐pathogen‐mortality in both males and females across all tested infectious doses. Our results therefore highlight that in addition to regulating an efficient pathogen clearance response, negative regulators of IMD also contribute to disease tolerance. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Rosacea is a chronic inflammatory disease, and doxycycline is a widely recommended treatment for it due to its anti‐inflammatory action. Oral isotretinoin reduces sebaceous gland activity and modulates toll‐like receptors, reducing inflammation. Our aim was to investigate the effect of these two drugs on the expression of cutaneous immunohistochemical biomarkers related to etiopathogenic factors involved in rosacea.We conducted a randomized, comparative, and evaluator‐blinded trial, including 40 participants with moderate and severe papulopustular and ocular rosacea. Participants were treated with doxycycline (DOXY) 100 mg or isotretinoin (ISO) 0.3 mg/kg daily. Immunohistochemistry at baseline and after 4 months was used to demonstrate the expression of the biomarker on the affected skin.The following changes were detected: a reduction in the vessel count after using VEGF with DOXY (P = 0.010); a decrease in VEGF intensity with ISO (P < 0.001) and DOXY (P = 0.020); a reduction of nitric oxide synthase enzyme with both drugs in the inflammatory infiltrate (ISO P < 0.001; DOXY P = 0.003); however, only with ISO was there a significant (P = 0.030) decrease at the level of the sebaceous glands, indicating a reduction of nitric oxide synthesis; a reduction of TRPV‐1 expression at the level of the sebaceous glands was observed only with DOXY (P = 0.041); a decrease of cathelicidin LL37 expression, a key antimicrobial peptide in the etiopathogenesis of rosacea, was noted with both drugs, although at the level of sebaceous glands, only with DOXY (P = 0.007).Oral isotretinoin and doxycycline have modified the expression of cutaneous biomarkers related to rosacea etiopathogenesis, demonstrating their role in controlling inflammatory and vascular processes. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) in insects are endogenous peptides that are effector components of the innate defense system of the insect. AMPs may serve as antimicrobial agents because of their small molecular weight and broad‐spectrum antimicrobial activity. In this study, we performed transcriptome analysis of cigarette beetle (Lasioderma serricorne) larvae, parasitized by the ectoparasitic wasp, Anisopteromalus calandrae. Several AMP genes were significantly upregulated following A. calandrae parasitism, postulating the hypothesis that the parasitization enhanced the host's resistance against pathogenic microorganisms through the regulation of host AMP genes. Specifically, 3 AMP genes (LsDef1, LsDef2, and LsCole) were significantly upregulated and we studied their immune function in L. serricorne. Immune challenge and functional analysis showed that LsCole was responsible for the immune response against Gram‐negative and Gram‐positive bacteria, while LsDef1 and LsDef2 were involved in insect defense against Gram‐positive bacteria. Purified recombinant LsCole exhibited antimicrobial activities against the Gram‐negative bacterium Escherichia coli and the Gram‐positive bacterium Staphylococcus aureus. LsDef2 showed an antibacterial effect against S. aureus. LsCole and LsDef2 exhibited antibiofilm activity against S. aureus. The 2 AMPs disrupted cell membranes and caused leakage of S. aureus cell contents. The results indicated that the 3 AMPs in L. serricorne are involved in the innate immunity of this pest insect. These AMPs may have potential as antimicrobial agents for bacterial infection chemotherapy. Hence, data are discussed in relation to new control strategies with greater biosafety against pest insects with use of microbial biocontrol agents in combination with RNA interference against the insect's defensive AMP genes. [ABSTRACT FROM AUTHOR]

Alarming sepsis‐related mortality rates present significant challenges to healthcare services globally. Despite advances made in the field, there is still an urgent need to develop innovative approaches that could improve survival rates and reduce the overall cost of treatment for sepsis patients. Therefore, this study aimed to develop a novel multifunctional therapeutic agent for advanced control of bacterial sepsis. Extracellular vesicles (EVs) isolated from lipopolysaccharide (LPS) induced HepG2 (hepatocellular carcinoma cells) (iEV) displayed an average particle size of 171.63 ± 2.77 nm, a poly dispersion index (PDI) of 0.32 ± 0.0, and a zeta potential (ZP) of −11.87 ± 0.18 mV. Compared to HepG2 EV, LPS induction significantly increases the EV protein concentration, PDI and ZP, reduces the average size and promotes cell proliferation and cytoprotective effects of the isolated EVs (iEVs) against LPS‐induced cytotoxicity. Coating of iEV with a cationic antimicrobial peptide (AMP) to form PC‐iEV slightly changed their physical properties and shifted their surface charge toward neutral values. This modification improved the antibacterial activity (2‐fold lower minimum bactericidal concentration [MBC] values) and biocompatibility of the conjugated peptide while maintaining iEV cytoprotective and anti‐inflammatory activities. Our findings indicate the superior anti‐inflammatory and antibacterial dual activity of PC‐iEV against pathogens associated with sepsis. [ABSTRACT FROM AUTHOR]

Summary: Antimicrobial peptides (AMPs) are emerging as next‐generation therapeutics due to their broad‐spectrum activity against drug‐resistant bacterial strains and their ability to eradicate biofilms, modulate immune responses, exert anti‐inflammatory effects and improve disease management. They are produced through solid‐phase peptide synthesis or in bacterial or yeast cells. Molecular farming, i.e. the production of biologics in plants, offers a low‐cost, non‐toxic, scalable and simple alternative platform to produce AMPs at a sustainable cost. In this review, we discuss the advantages of molecular farming for producing clinical‐grade AMPs, advances in expression and purification systems and the cost advantage for industrial‐scale production. We further review how 'green' production is filling the sustainability gap, streamlining patent and regulatory approvals and enabling successful clinical translations that demonstrate the future potential of AMPs produced by molecular farming. Finally, we discuss the regulatory challenges that need to be addressed to fully realize the potential of molecular farming‐based AMP production for therapeutics. [ABSTRACT FROM AUTHOR]

ABSTRACT Antimicrobial peptides (AMPs) are being studied for their potential in addressing microbial resistance, a significant issue in treating infections. More than 22,500 AMPs are listed in the database, but their clinical use faces challenges like instability and selectivity. Nanodrug delivery systems are now seen as a beneficial method to improve the effectiveness of AMPs. These systems can shield AMPs from degradation, enhance their availability, and deliver them to specific infection sites, enhancing their ability to combat resistance. One example is liposomal nanoparticles loaded with a mix of AMPs, targeting drug‐resistant bacteria directly. Strategies to develop novel AMPs through engineering methods, including design approaches, computational techniques, and modifications for stability, are discussed in this review. Combinatorial approaches with antibiotics, patents, and clinical trials involving AMPs against infections are also considered, highlighting the potential of AMPs in battling microbial resistance. [ABSTRACT FROM AUTHOR]

Background: Fish skin mucus contains innate immune factors and acts as the first line of physical or chemical defense against pathogens. Objective: The primary aim of this study was to determine the antiviral activity of sea bream (SBr), rainbow trout (RT), and sea bass (SBa) fish skin mucus against herpes simplex virus (HSV)‐1. In addition, it was aimed to associate possible antiviral activity with antimicrobial peptides (AMPs) such as cathelicidin, hepcidin, galectin 2, and C10ORF99, whose levels were determined in the mucus. Methods: The antiviral activity and oxidative/antioxidant status of mucus against HSV‐1 virus was evaluated. In addition, AMPs, SOD, and CAT activities, and immunoglobulin M levels were also analyzed in mucus of fish. Results: Antiviral activity mucus of SBr, RT, and SBa against HSV‐1 were determined as 2−4, 2−5, and 2−2, respectively. The higher antiviral activity of SBr and RT mucus compared to the mucus of SBa can be associated with higher AMP levels in them. Conclusion: The skin mucus of SBr and RT may be nutritional supplement, adjuvant, and a new agent that can potentiate the effects of antimicrobial/antiviral agents. [ABSTRACT FROM AUTHOR]

Marine biofouling poses a major challenge to ship navigation and hinders the development of the shipping industry. Urgent action is required to tackle this problem through the implementation of innovative strategies. Antimicrobial peptides have garnered considerable attention due to their outstanding effectiveness, wide range of activity, and eco‐friendly characteristics. This study involved grafting the antibacterial peptide andricin 01 (AIGHCLGATL) onto the surface of an aluminum alloy, thereby creating a modified surface with antibacterial properties. In summary, amino groups were introduced onto the surface of aluminum alloys through the silanization process using (3‐aminopropyl) triethoxysilane (APTES), and then the peptides were covalently immobilized on the treated surface using glutaraldehyde as a cross‐linking agent. The successful modification of the peptide was confirmed by Fourier transform‐infrared spectroscopy (FT‐IR) and X‐ray photoelectron spectroscopy (XPS) analysis. The antimicrobial peptide‐modified aluminum alloy surfaces exhibited significant bactericidal activity, killing 75.3% of Bacillus sp. and 85.5% of Escherichia coli, while achieving antifouling efficiencies of 88.6% and 90.7% against Bacillus sp. and E. coli, respectively. Furthermore, molecular dynamics simulations showed that the inserted of the peptides into the phospholipid membrane caused a change in the local membrane curvature, which eventually led to membrane rupture. These results provide valuable information for the application of antimicrobial peptides in the field of antifouling and the elucidation of antifouling mechanisms. [ABSTRACT FROM AUTHOR]

Background and Purpose: The interleukin (IL)‐36 pathway is a critical player in the pathogenesis of pustular psoriasis. However, therapies targeting this pathway are limited or unaffordable (e.g. the anti‐IL‐36 receptor antibody). AMP‐activated protein kinase (AMPK), a regulator of cellular energy and metabolism, is known to participate in inflammatory diseases. However, its role in IL‐36‐induced skin inflammation remains unclear. Therefore, we sought to investigate the role of AMPK signals in regulating IL‐36‐induced responses in the skin. Experimental Approach: IL‐36‐stimulated primary normal human epidermal keratinocytes (NHEKs) and IL‐36‐injected (intradermally) BALB/c mice served as the cell and animal models, respectively. Additionally, 5‐aminoimidazole‐4‐carboxamide riboside (AICAR) and A769662 served as AMPK activators. Key Results: AICAR and A769662 significantly suppressed the IL‐36‐induced IL‐8 (CXCL8) and CCL20 production from NHEKs. IL‐36‐induced IκBζ protein expression was prominently reduced and IKK/IκBα phosphorylation was attenuated by AICAR and A769662. Conversely, AMPKα knockdown increased IκBζ protein expression and IKK/IκBα phosphorylation in IL‐36‐treated NHEKs. Furthermore, AICAR and A769662 enhanced IL‐36‐induced‐IκBζ protein degradation via the proteasome‐dependent but not the lysosome‐dependent pathway. Pretreatment of NHEKs with IL‐36 slightly suppressed the AICAR‐ and A769662‐triggered phosphorylation of AMPK and acetyl‐CoA carboxylase. In the mouse model, topical application of AICAR significantly reduced ear swelling, redness, epidermal thickening, neutrophil infiltration and inflammatory and antimicrobial peptide gene expression. Conclusion and Implications: AMPK activation suppresses IL‐36‐induced IL‐8 and CCL20 release by regulating IκBζ expression in keratinocytes and reduces IL‐36‐induced skin inflammation in mice, suggesting that AMPK activation is a potential strategy for treating patients with IL‐36‐mediated inflammatory skin disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: Insects mainly rely on innate immunity against pathogen infection. Plagiodera versicolora (Coleoptera: Chrysomelidae), is a worldwide leaf‐eating forest pest in salicaceous trees. However, the mechanisms behind the immunodeficiency pathway (IMD) remain poorly understood. RESULTS: In this study, we obtained a Relish gene from transcriptome analysis. Tissue and instar expression profiles were subsequently obtained using quantitative real‐time polymerase chain reaction analysis. The results showed that Relish has high expression levels in eggs, larvae and adults, and especially in fat bodies. Transcripts of the tested antimicrobial peptides (AMPs), defensin1, defensin2 and attacin2 were downregulated by dsRelish. Knockdown of Relish led to greater mortality in larvae after Staphylococcus aureus infection. In addition, we performed bacterial 16S ribosomal RNA‐based high‐throughput sequencing. The results showed that the relative abundance of some gut bacteria was significantly altered after dsRelish ingestion. CONCLUSION: This study provides a greater understanding of the IMD signaling pathway, facilitating functional studies of Relish in P. versicolora. Moreover, a genetic pest management technique might be developed using Relish as a lethal gene to control the pest P. versicolora. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The silicifying peptide R5 (H‐SSKKSGSYSGSKGSKRRIL‐OH) derived from diatoms is extensively investigated, but the mechanism underlying silica synthesis by R5 or R5‐alike peptides is still poorly understood, limiting the design of silicifying peptides Herein, machine learning techniques are used to design peptides with silicifying functionality. Utilizing a comprehensive dataset of peptides and their corresponding silicification outcomes, a deep learning model based on antimicrobial peptide migration learning is created. This model exhibits the remarkable capability to accurately predict peptide sequences with a high potential for facilitating silica formation. A selection of artificially designed peptides can catalyze the biomimetic synthesis of nanosilica, some of which demonstrate better catalytic activity with a wider pH range and faster reaction rate compared with the peptide R5. Additionally, the designed peptide is used to wrap the model diatom Phaeodactylum tricornutum with nanosilica coatings, resulting in a significant enhancement in the UV resistance of cells. The new silicified peptides are highly significant for advancing the understanding of the silica synthesis mechanism in diatoms, and the encapsulation of P. tricornutum has potential benefits in the development of new biosensors. [ABSTRACT FROM AUTHOR]

To survive in the host, pathogenic bacteria need to be able to react to the unfavorable conditions that they encounter, like low pH, elevated temperatures, antimicrobial peptides and many more. These conditions may lead to unfolding of envelope proteins and this may be lethal. One of the mechanisms through which bacteria are able to survive these conditions is through the protease/foldase activity of the high temperature requirement A (HtrA) protein. The gut pathogen Clostridioides difficile encodes one HtrA homolog that is predicted to contain a membrane anchor and a single PDZ domain. The function of HtrA in C. difficile is hitherto unknown but previous work has shown that an insertional mutant of htrA displayed elevated toxin levels, less sporulation and decreased binding to target cells. Here, we show that HtrA is membrane associated and localized on the surface of C. difficile and characterize the requirements for proteolytic activity of recombinant soluble HtrA. In addition, we show that the level of HtrA in the bacteria heavily depends on its proteolytic activity. Finally, we show that proteolytic activity of HtrA is required for survival under acidic conditions. [ABSTRACT FROM AUTHOR]

Inspired by the broad spectrum of antimicrobial activity exhibited by Magainins and SMAP‐28, and based on their chemical structures, several linear peptides were designed and synthesized with the aim of achieving peptides possessing promising anti‐chlamydial activity with lower cytotoxicity towards human normal cell lines. We found these peptides to be cytotoxic against human normal cell lines, except for one designated as DJ‐7, which was utilized in subsequent experiments, while the others were excluded. Peptide DJ‐7 was readily synthesized using standard Fmoc‐SPPS, and its anti‐chlamydial activity was investigated against HeLa cells (ATCC CCL‐2) infected with Chlamydia trachomatis L2 (ATCC VR‐902B) at MOI 1 for 2 hours, followed by treatment with increasing concentrations of peptide DJ‐7 (15–60 μg/mL). Microscopic examination revealed a significant reduction in the total number of bacterial inclusions in cells by around 50 % and 80 % after treatment with 15 μg/mL (5.5 μM) and 30 μg/mL (11 μM) of peptide DJ‐7, respectively, compared to control untreated infected cells. The impact of peptide DJ‐7 treatment on the development of infectious C. trachomatis serovar L2 progeny was investigated, demonstrating a significant decrease in infectious chlamydia after treatment with peptide DJ‐7. This suggests that chlamydia failed to complete its typical developmental cycle, indicating that peptide DJ‐7 exhibits anti‐chlamydial properties, by disrupting the normal bacterial development process. Our results indicate that peptide DJ‐7 is a promising lead peptide for further development as a potential anti‐chlamydial agent. [ABSTRACT FROM AUTHOR]

Epinecidin‐1 (epi‐1), an antimicrobial peptide first identified in marine grouper fish, has multifunctional bioactivities. The present study aims to improve its therapeutic potential via structural modifications that could enhance its antimicrobial activity and stability. To achieve it, we replaced glycine and the first histidine in the parent epi‐1 with lysine, which resulted in a peptide with a repeating KXXK motif and improved physiochemical properties related to antimicrobial activity. This modified peptide, referred to as glycine‐to‐lysine replaced‐epi‐1, also gained stability and a twofold increase in helical propensity. To produce the active peptide, overlap extension PCR was employed to generate the gene of GK‐epi‐1 via site‐directed mutagenesis, which was then cloned into the pET‐32a vector and expressed as a recombinant fusion protein in Escherichia coli C43 (DE3) strain. The recombinant protein was purified and digested with enterokinase to release the active peptide fragment, which was then evaluated for antimicrobial activity and stability. The lysine substitution led to an enhancement in broad‐spectrum antimicrobial activity against a wide range of nosocomial pathogenic bacteria. [ABSTRACT FROM AUTHOR]

There is considerable evidence showing that highly ordered aggregate structures known as amyloids carry out essential biological roles in species ranging from bacteria to humans. Indeed, many antimicrobial peptides/proteins form amyloids to carry out their host defense functions and many amyloids are antimicrobial. The similarity of host defense amyloids from bacterial biofilms to the mammalian epididymal amyloid matrix implies highly conserved host defense structures/functions. With an emphasis on the epididymal amyloid matrix, here we review the common properties of host defense amyloids including unique traits that would allow them to function as powerful biosensors of the immune system. [ABSTRACT FROM AUTHOR]

Endodontic therapy includes various procedures such as vital pulp therapy, root canal treatment and retreatment, surgical endodontic treatment and regenerative endodontic procedures. Disinfection and tissue repair are crucial for the success of these therapies, necessitating the development of therapeutics that can effectively target microbiota, eliminate biofilms, modulate inflammation and promote tissue repair. However, no current endodontic agents can achieve these goals. Antimicrobial peptides (AMPs), which are sequences of amino acids, have gained attention due to their unique advantages, including reduced susceptibility to drug resistance, broad‐spectrum antibacterial properties and the ability to modulate the immune response of the organism effectively. This review systematically discusses the structure, mechanisms of action, novel designs and limitations of AMPs. Additionally, it highlights the efforts made by researchers to overcome peptide shortcomings and emphasizes the potential applications of AMPs in endodontic treatments. [ABSTRACT FROM AUTHOR]

Summary: This study delved into the antimicrobial potential of hydrolysates from adzuki bean and mung bean protein concentrates, created using Alcalase and Flavourzyme enzymes. Targeting common foodborne pathogens (Salmonella Typhimurium, Salmonella Enteritidis, Vibrio parahaemolyticus, Staphylococcus aureus, and Bacillus subtilis) and Escherichia coli, the research underscored the crucial role of peptidase in generating antibacterial peptides. Fractions F2 of Flavourzyme hydrolysed adzuki bean (ABF) and F4 of Flavourzyme hydrolysed mung bean (MBF) showed the highest antibacterial activity against S. Typhimurium and S. aureus, respectively, whereas F2 of Alcalase hydrolysed mung bean (MBA) exhibited very poor activity against S. aureus. TripleTOF LC–MS/MS analysis revealed small cationic antibacterial peptides, with lysine being prominent against S. aureus and proline–proline against S. Typhimurium. These findings highlighted the significant contribution of protease enzymes in fostering antibacterial peptide production, offering valuable insights for developing effective antimicrobial agents in the context of food safety. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effects of antimicrobial peptides (AMPs) on Stage III Grade B periodontitis. Methods: This trial abided by the principle of consistency test, approved by ethics committee and registered in clinical trials. All qualified 51 patients with Stage III Grade B periodontitis were randomly divided into three groups: SRP group, SRP with minocycline hydrochloride (Mino group) as Control groups, and SRP with AMPs (AMP group) as the Test group. Clinical examinations and subgingival plaques were monitored at baseline and at 7 and 90 days after treatment in the SRP, SRP with AMP and Mino groups. Results: The AMP group (Test group) had a reduced PD (Periodontal probing depth) and an attachment gain significantly higher than SRP and Mino groups (Control groups) at day 90. The abundance of periodontal pathogens was decreased in the AMP group at 7 and 90 days compared with the SRP group and Mino group. Only the AMP group showed an increase the abundance of periodontal probiotics including Capnocytophaga, Gemella, and Lactobacillus at 7 and 90 days. Conclusions: This study shows that AMPs as an adjunct to SRP promote additional clinical and microbiological benefits in the treatment of Stage III Grade B periodontitis. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) poses a serious threat to human health worldwide. It is now more challenging than ever to introduce a potent antibiotic to the market considering rapid emergence of antimicrobial resistance, surpassing the rate of antibiotic drug discovery. Hence, new approaches need to be developed to accelerate the rate of drug discovery process and meet the demands for new antibiotics, while reducing the cost of their development. Machine learning holds immense promise of becoming a useful tool, especially since in the last two decades, exponential growth has occurred in computational power and biological big data analytics. Recent advancements in machine learning algorithms for drug discovery have provided significant clues for potential antibiotic classes. Apart from discovery of new scaffolds, the machine learning protocols will significantly impact prediction of AMR patterns and drug metabolism. In this review, we outline power of machine learning in antibiotic drug discovery, metabolic fate, and AMR prediction to support researchers engaged and interested in this field. [ABSTRACT FROM AUTHOR]

Diverse computational approaches have been widely used to assist in designing antimicrobial peptides with enhanced activities. This tactic has also been used to address the need for new treatment alternatives to combat resistant bacterial infections. Herein, we have designed eight variants from a natural peptide, pro‐adrenomedullin N‐terminal 20 peptide (PAMP), using an in silico pattern insertion approach, the Joker algorithm. All the variants show an α‐helical conformation, but with differences in the helix percentages according to circular dichroism (CD) results. We found that the C‐terminal portion of PAMP may be relevant for its antimicrobial activities, as revealed by the molecular dynamics, CD, and antibacterial results. The analogs showed variable antibacterial potential, but most were not cytotoxic. Nevertheless, PAMP2 exhibited the most potent activities against human and animal‐isolated bacteria, showing cytotoxicity only at a substantially higher concentration than its minimal inhibitory concentration (MIC). Our results suggest that the enhanced activity in the profile of PAMP2 may be related to their particular physicochemical properties, along with the adoption of an amphipathic α‐helical arrangement with the conserved C‐terminus portion. Finally, the peptides designed in this study can constitute scaffolds for the design of improved sequences. [ABSTRACT FROM AUTHOR]

The development of new radiopharmaceuticals for the detection of hidden infection foci has great relevance for early detection and the selection of the correct treatment, particularly in immunosuppressed patients. In that sense, the labelling of antimicrobial peptides (AMPs) that are capable of binding specifically to the pathogenic microorganism which causes the infection, should provide a sufficiently specific agent, able to distinguish an infection from a sterile inflammation. Defensins are particularly interesting molecules with antimicrobial activity, the EcgDf1 defensin was identified from the genome of a Uruguayan native plant, Erythrina crista‐galli, the 'Ceibo' tree. Our group has previously reported a synthetic biologically active short analogue EcgDf21 (ERFTGGHCRGFRRRCFCTKHC) successfully labelled with 99mTc. Herein we present a shorter analogue which also preserves the γ‐core domain, as a pharmacophore for a potential infection detection agent. This peptide was derivatized with the bifunctional chelating agent 1,4,7‐triazacyclononane‐1,4,7‐triacetic acid (NOTA) through a lysine linker in the amino‐terminal group (NOTA‐KGHCRGFRRRC) and radiolabelled with 68Ga ([68Ga]Ga‐NOTA‐K‐EcgDf1(10)). The [68Ga]Ga‐NOTA‐K‐EcgDf1(10) labelling procedure rendered a product with high radiochemical purity and stability in the labelling milieu. The Log P value indicated that the complex has a hydrophilic behaviour, confirmed by the biodistribution profile. The [68Ga]Ga‐NOTA‐K‐EcgDf1(10) complex demonstrated specific binding to cultures of Candida albicans and Aspergillus niger. Its biodistribution showed renal elimination and low accumulation in the rest of the body. It was possible to successfully differentiate sterile inflammation from infection by PET images in nude mice with a target/non‐target ratio of 3.3 for C. albicans and 3.7 for A. niger, respectively. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis and Fusobacterium nucleatum are known to contribute to a variety of tumorigenic pathways linked to the progression of oral squamous cell carcinoma (OSCC). The growing global incidence of antibiotic resistance highlights the critical need to consider the use of antimicrobial peptides (AMPs) as a viable alternative to conventional antibiotics. The current study comprehensively tested Lactobacillus sp.−derived AMPs against bacterially exacerbated OSCC. A total of 52 AMPs were obtained from various databases, and an in silico analysis determined their potent antibacterial and anticancer characteristics after a rigorous screening and pruning approach. Twelve AMPs were tested for 3D structural alignment prediction and validation, with the GH12 synthetic AMP serving as a control. These candidate peptides were thoroughly screened against six important virulence proteins of P. gingivalis and four of F. nucleatum, with the lowest energy score of the docked complexes measuring binding affinity and interactions with active residues being chosen. plpl_18 was determined as the most efficient new AMP that interacted with the virulence protein RagB of P. gingivalis and Fap2 of F. nucleatum with docking scores of −238.24 and −254.27 kcal/mol, respectively. This AMP plpl_18 was docked against selective target OSCC regulatory proteins such as cytokines, metallomatrix proteinase, MAPK, E‐cadherin, and JAK‐1 proteins. Among these proteins, it docked against matrix metalloproteinase‐9 with the highest negative docking scores of −7.5, −260.956, and −1361.9 kcal/mol using AutoDock Vina, HPEPDOCK, and ClusPro 2.0, respectively. Molecular dynamic simulation was used to perform extrapolated validation. These computational studies provide an essential foundation for anticipated laboratory and clinical investigations concerning the possibility of adapting therapeutic peptides based on probiotics to combat the proliferation of OSCC, which is accelerated by F. nucleatum and P. gingivalis. [ABSTRACT FROM AUTHOR]

Wasps have been neglected in toxinological studies, even with their diversity of species, when compared to other groups of venomous animals such as snakes, scorpions, and spiders. Solitary wasps, such as Pepsis decorata, are known for their mechanism of total or temporary paralysis of the host. In addition, their venoms are considered sources for studies of small peptides, bioactive peptides with neural and antimicrobial activities. In this work, some oligopeptides were analyzed by de novo sequencing identifying 39 oligopeptide sequences. Some sequences were similar to proctolin, a bradykinin‐potentiating peptide, and poneritoxin, one bradykinin‐related peptide. As proctolin‐like peptides were the major constituent in distinct experimental conditions, it was selected for further in silico studies in order to understand its possible importance as a constituent of wasp venom and whether these peptides could be of biotechnological importance. We investigate its binding mode comparing with proctolin and we further analyzed the importance of the tyrosine‐leucine‐glutamic acid (YLE) tripeptide‐motif conservation. This experimental, an in silico approach, increased the range of compounds identified in peptide analyses proving good characterization of little‐known peptidic compounds. [ABSTRACT FROM AUTHOR]

In the realm of therapeutic peptides, tremendous progress has been achieved in the last two decades. The building block of peptides that is, 'Amino Acid' has been modified by various chemical modifications such as side‐chain alteration in linear peptides, cyclization, back‐bone modification, pro‐drug moiety, conjugation with heterocycles, and natural products to make peptides a foremost candidate as a therapeutic drug. Since the advent of insulin in 1922, peptides have immensely affected the development of the pharmaceutical industry giving rise to the peptide‐based drug industry. In recent years, peptides having antimicrobial, antiviral, anti‐tumor, anti‐inflammatory, anti‐aging, and antioxidant properties have developed. Also, it has now entered as a potent candidate in the field of oncology and also become a valuable tool as a radiolabeled peptide for the detection of various diseases. Generally, peptides were extracted from natural sources in the olden days, but presently work is directed towards finding alternate and sustainable ways for developing synthetic peptides. The present review covers the discussion about the historic evaluation of peptides, available effective synthetic processes, current advancements, use of bioinformatic tools, computational strategies, and the methodology to overcome the barrier for making peptides the potent candidate for the future world. [ABSTRACT FROM AUTHOR]

In the present study, we identified and characterized two defensin‐like peptides in an antifungal fraction obtained from Capsicum chinense pepper fruits and inhibited the growth of Colletotrichum scovillei, which causes anthracnose. AMPs were extracted from the pericarp of C. chinense peppers and subjected to ion exchange, molecular exclusion, and reversed‐phase in a high‐performance liquid chromatography system. We investigated the endogenous increase in reactive oxygen species (ROS), the loss of mitochondrial functioning, and the ultrastructure of hyphae. The peptides obtained from the G3 fraction through molecular exclusion chromatography were subsequently fractionated using reverse‐phase chromatography, resulting in the isolation of fractions F1, F2, F3, F4, and F5. The F1‐Fraction suppressed C. scovillei growth by 90, 70.4, and 44% at 100, 50, and 25 μg mL−1, respectively. At 24 h, the IC50 and minimum inhibitory concentration were 21.5 μg mL−1 and 200 μg mL−1, respectively. We found an increase in ROS, which may have resulted in an oxidative burst, loss of mitochondrial functioning, and cytoplasm retraction, as well as an increase in autophagic vacuoles. MS/MS analysis of the F1‐Fraction indicated the presence of two defensin‐like proteins, and we were able to identify the expression of three defensin sequences in our C. chinense fruit extract. The F1‐Fraction was also found to inhibit the activity of insect α‐amylases. In summary, the F1‐Fraction of C. chinense exhibits antifungal activity against a major pepper pathogen that causes anthracnose. These defensin‐like compounds are promising prospects for further research into antifungal and insecticide biotechnology applications. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a critical public health concern, necessitating the exploration of alternative treatments. While antimicrobial peptides (AMPs) show promise, assessing their toxicity using traditional wet lab methods is both time‐consuming and costly. We introduce tAMPer, a novel multi‐modal deep learning model designed to predict peptide toxicity by integrating the underlying amino acid sequence composition and the three‐dimensional structure of peptides. tAMPer adopts a graph‐based representation for peptides, encoding ColabFold‐predicted structures, where nodes represent amino acids and edges represent spatial interactions. Structural features are extracted using graph neural networks, and recurrent neural networks capture sequential dependencies. tAMPer's performance was assessed on a publicly available protein toxicity benchmark and an AMP hemolysis data we generated. On the latter, tAMPer achieves an F1‐score of 68.7%, outperforming the second‐best method by 23.4%. On the protein benchmark, tAMPer exhibited an improvement of over 3.0% in the F1‐score compared to current state‐of‐the‐art methods. We anticipate tAMPer to accelerate AMP discovery and development by reducing the reliance on laborious toxicity screening experiments. [ABSTRACT FROM AUTHOR]

ABSTRACT This review examines the potential applications of peptides in biotechnology, medicine, and pharmacy, while highlighting the important antibacterial and antiviral properties of peptides. Peptides and chemical peptide synthesis have become a field of study that is gaining great momentum today. Some of the main reasons for this are high specificity, biodegradability and versatility of peptides. Peptides also have some specific properties that make them attractive for pharmaceutical development. As a case study, it can be used to create peptides that can be used to replace or fix damaged proteins in the body by mimicking the action of naturally occurring proteins. Delivering drugs or other therapeutic agents to specific cells or tissues is another method that can help increase the effectiveness of treatment and reduce unwanted effects. Various types of antimicrobial peptides (AMPs), such as defensins and cathelicidins, and their anti‐infective properties are also discussed. Finally, peptides (melittin, lactoferricin, etc.) can be used to trigger an immune response against certain infections, such as COVID‐19 and Zika virus, by acting as vaccines. In our study, a comprehensive review was made on antiviral and AMPs, and especially peptides containing arginine and lysine were mentioned. The properties of these peptides, examples of these peptides and their developments in the pharmaceutical field are emphasized. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a global healthcare challenge that urgently needs the development of new therapeutic agents. Antimicrobial peptides and mimics thereof are promising candidates but mostly suffer from inherent toxicity issues due to the non‐selective binding of cationic groups with mammalian cells. To overcome this toxicity issue, this work herein reports the synthesis of a smart antimicrobial dendron with masked cationic groups (Gal‐Dendron) that could be uncaged in the presence of β‐galactosidase enzyme to form the activated Enz‐Dendron and confer antimicrobial activity. Enz‐Dendron show bacteriostatic activity toward Gram‐negative (P. aeruginosa and E. coli) and Gram‐positive (S. aureus) bacteria with minimum inhibitory concentration values of 96 µm and exerted its antimicrobial mechanism via a membrane disruption pathway, as indicated by inner and outer membrane permeabilization assays. Crucially, toxicity studies confirmed that the masked prodrug Gal‐Dendron exhibited low hemolysis and is at least 2.4 times less toxic than the uncaged cationic Enz‐Dendron, thus demonstrating the advantage of masking the cationic groups with responsive immolative linkers to overcome toxicity and selectivity issues. Overall, this study highlights the potential of designing new membrane‐disruptive antimicrobial agents that are more biocompatible via the amine uncaging strategy. [ABSTRACT FROM AUTHOR]

The misuse of antibiotics has led to antibiotic‐resistant "superbugs," prompting the exploration of alternative antibacterial strategies. This study focuses on the promising avenue of photothermal therapy (PTT). Despite numerous advantages, the clinical applicability of PTT as a sole sterilization strategy is hindered by the necessity for higher temperatures, potentially causing harm to healthy tissues. To overcome this challenge, this study introduces antimicrobial peptides (AMPs) to modify the surface of gallium‐based liquid metal (LM) nano‐antimicrobial agents, thereby enhancing their photothermal antibacterial effects within a lower temperature range. First, a novel LM composite nanomaterial, LM@AMP nanoparticles, is synthesized through a sonication process involving 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[carboxy(polyethylene glycol)], AMP, and LM in an aqueous solution. Herein, AMPs not only contribute to the structural stability of LM nanoparticles but also enhance their selective interaction with bacterial cell membranes. Then, a thorough characterization of LM@AMP nanoparticles is performed, encompassing analyses through electron microscopy, determination of particle size, and assessment of zeta potential. Moreover, the exceptional photothermal properties exhibited by these nanoparticles are validated. Finally, this investigation demonstrates that LM@AMP nanoparticles selectively target bacterial cell membranes, showcasing efficient bactericidal effects (near 100%) at relatively low temperatures under near‐infrared irradiation. [ABSTRACT FROM AUTHOR]

This article discusses the activation of mast cells (MCs) through the Mas-related G protein-coupled receptor X2 (MRGPRX2) pathway. The study focuses on the chemokine CXCL17, which is expressed in mucosal tissues and has antimicrobial properties. The researchers found that CXCL17 activates human MCs via the MRGPRX2 pathway, and this activation may be important in inflammatory conditions such as psoriasis. The study also provides evidence of increased expression of CXCL17 in psoriatic skin, particularly in areas proximal to MRGPRX2-positive MCs. Further research is needed to understand the role of CXCL17-induced MC activation in psoriasis and other inflammatory skin diseases. [Extracted from the article]

Enterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope‐acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two‐component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. To better understand the regulation of DAP resistance and how this relates to mutations observed in DAP‐resistant clinical isolates of enterococci, we here explored the interplay between these two regulatory pathways. Our results show that SapR regulates an additional resistance operon, dltXABCD, a known DAP resistance determinant, and show that LiaFSR regulates the expression of sapRS. This regulatory structure places SapRS‐target genes under dual control, where expression is directly controlled by SapRS, which itself is up‐regulated through LiaFSR. The network structure described here shows how Enterococcus faecalis coordinates its response to cell envelope attack and can explain why clinical DAP resistance often emerges via mutations in regulatory components. [ABSTRACT FROM AUTHOR]

Insects rely on their innate immune system to eliminate pathogenic microbes. As a system component, cytokines transmit intercellular signals to control immune responses. Growth‐blocking peptide (GBP) is a member of the stress‐responsive peptide family of cytokines found in several orders of insects, including Drosophila. However, the physiological role of GBP in defence against pathogens is not thoroughly understood. In this study, we explored the functions of GBP in a lepidopteran pest, Ostrinia furnacalis. Injection of recombinant O. furnacalis GBP (OfGBP) precursor (proGBP) and chemically synthesised GBP significantly induced the transcription of antimicrobial peptides (AMPs) and other immunity‐related genes including immune deficiency (IMD) and Dorsal. The level of OfGBP mRNA was upregulated after bacterial infection. Knockdown of OfGBP expression led to a decrease in IMD, Relish, MyD88 and Dorsal mRNA levels. OfGBP induced phenoloxidase activity and affected hemocyte behaviours in O. furnacalis larvae. In summary, GBP is a potent cytokine, effectively regulating AMP synthesis, melanization response and cellular immunity to eliminate invading pathogens. [ABSTRACT FROM AUTHOR]

Parasitoids are important components of the natural enemy guild in the biological control of insect pests. They depend on host resources to complete the development of a specific stage or whole life cycle and thus have evolved towards optimal host exploitation strategies. In the present study, we report a specific survival strategy of a fly parasitoid Exorista sorbillans (Diptera: Tachinidae), which is a potential biological control agent for agricultural pests and a pest in sericulture. We found that the expression levels of nitric oxide synthase (NOS) and nitric oxide (NO) production in host Bombyx mori (Lepidoptera: Bombycidae) were increased after E. sorbillans infection. Reducing NOS expression and NO production with an NOS inhibitor (NG‐nitro‐L‐arginine methyl ester hydrochloride) in infected B. mori significantly impeded the growth of E. sorbillans larvae. Moreover, the biosynthesis of 20‐hydroxyecdysone (20E) in infected hosts was elevated with increasing NO production, and inhibiting NOS expression lowered 20E biosynthesis. More importantly, induced NO synthesis was required to eliminate intracellular bacterial pathogens that presumably competed for shared host resources. Inhibiting NOS expression down‐regulated the transcription of antimicrobial peptide genes and increased the number of bacteria in parasitized hosts. Collectively, this study revealed a new perspective on the role of NO in host–parasitoid interactions and a novel mechanism for parasitoid regulation of host physiology to support its development. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) manifests clinically with chronic intestinal inflammation and microflora dysbiosis. Although biologics can effectively control inflammation, efficient delivery to the colon and colon epithelial cells remains challenging. Milk‐derived extracellular vesicles (EV) show promise as an oral delivery tool, however, the ability to load biologics into EV presents challenges to therapeutic applications. Here, we demonstrate that fusing cell‐penetrating peptide (TAT) to green fluorescent protein (GFP) enabled biologics loading into EV and protected against degradation in the gastrointestinal environment in vitro and in vivo after oral delivery. Oral administration of EV loaded with anti‐tumour necrosis factor‐α (TNF‐α) nanobody (VHHm3F) (EVVHH) via TAT significantly reduced tissue TNF‐α levels and alleviated pathologies in mice with acute UC, compared to VHH alone. In mice with chronic UC, simultaneously introducing VHH and an antimicrobial peptide LL37 into EV (EVLV), then administering orally improved intestinal barrier, inflammation and microbiota balance, resulted in relief of UC‐induced depression and anxiety. Collectively, we demonstrated that oral delivery of EVLV effectively alleviated UC in mice and TAT efficiently loaded biologics into EV to confer protection from degradation in the gastrointestinal tract. This therapeutic strategy is promising for UC and is a simple and generalizable approach towards drug‐loaded orally‐administrable EV treatment for other diseases. [ABSTRACT FROM AUTHOR]

This concept paper elucidates the possible influence of the electrical double layer (EDL) and the polyelectrolytic nature of bacterial cell walls on the behavior of antimicrobial peptides (AMPs) and lipopeptides. It proposes that the presence of EDL adjacent to lipid membranes may play a crucial role in inducing peptide aggregation and conformational changes, thus affecting their antimicrobial activity. Furthermore, it emphasizes that the negatively charged components in both Gram‐positive and Gram‐negative bacterial cell walls may act as polyelectrolytes, effectively reducing the critical micellization concentration (CMC) of positively charged peptides and lipopeptides. This reduction is expected to facilitate their aggregation, potentially enhancing their accumulation at the bacterial membrane and increasing their effectiveness in disrupting membrane integrity and exerting antimicrobial activity. Therefore, understanding the interplay between EDL effects, polyelectrolytic properties of bacterial cell walls, and the behavior of antimicrobial peptides is essential for elucidating their mechanisms of action and optimizing their therapeutic potential. [ABSTRACT FROM AUTHOR]

The rise of antimicrobial resistance and multi‐drug resistant pathogens has necessitated explorations for novel antibiotic agents as the discovery of conventional antibiotics is becoming economically less viable and technically more challenging for biopharma. Antimicrobial peptides (AMPs) have emerged as a promising alternative because of their particular mode of action, broad spectrum and difficulty that microbes have in becoming resistant to them. The AMPs bacitracin, gramicidin, polymyxins and daptomycin are currently used clinically. However, their susceptibility to proteolytic degradation, toxicity profile, and complexities in large‐scale manufacture have hindered their development. To improve their proteolytic stability, methods such as integrating non‐canonical amino acids (ncAAs) into their peptide sequence have been adopted, which also improves their potency and spectrum of action. The benefits of ncAA incorporation have been made possible by solid‐phase peptide synthesis. However, this method is not always suitable for commercial production of AMPs because of poor yield, scale‐up difficulties, and its non‐'green' nature. Bioincorporation of ncAA as a method of integration is an emerging field geared towards tackling the challenges of solid‐phase synthesis as a green, cheaper, and scalable alternative for commercialisation of AMPs. This review focusses on the bioincorporation of ncAAs; some challenges associated with the methods are outlined, and notes are given on how to overcome these challenges. The review focusses particularly on addressing two key challenges: AMP cytotoxicity towards microbial cell factories and the uptake of ncAAs that are unfavourable to them. Overcoming these challenges will draw us closer to a greater yield and an environmentally friendly and sustainable approach to make AMPs more druggable. [ABSTRACT FROM AUTHOR]

Recently, the discovery of antimicrobial peptides (AMPs) as excellent candidates for overcoming antibiotic resistance has attracted significant attention. AMPs are short peptides active against bacteria, cancer cells, and viruses. It has been shown that the SARS‐CoV‐2 nucleocapsid protein (N−P) undergoes liquid‐liquid phase separation in the presence of RNA, resulting in biocondensate formation. These biocondensates are crucial for viral replication as they concentrate the viral RNA with the host cell's protein machinery required for viral protein expression. Thus, N−P biocondensates are promising targets to block or slow down viral RNA transcription and consequently virion assembly. We investigated the ability of three AMPs to interfere with N−P/RNA condensates. Using microscopy techniques, supported by biophysical characterization, we found that the AMP LL–III partitions into the condensate, leading to clustering. Instead, the AMP CrACP1 partitions into the droplets without affecting their morphology but reducing their dynamics. Conversely, GKY20 leads to the formation of fibrillar structures after partitioning. It can be expected that such morphological transformation severely impairs the normal functionality of the N−P droplets and thus virion assembly. These results could pave the way for the development of a new class of AMP‐based antiviral agents targeting biocondensates. [ABSTRACT FROM AUTHOR]