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BACKGROUND: Cationic antimicrobial peptides (AMPs) possess broad‐spectrum biological activities with less inclination to inducing antibiotic resistance. Herein a battery of amphiphilic amidines were designed by mimicking the characteristics of AMPs. The antifungal activities and the effects to the hyphal morphology and membrane permeability were investigated. RESULTS: The results indicated the inhibitory rates of ten compounds were over 80% to Botrytis cinerea and ten compounds over 90% to Valsa mali Miyabe et Yamada at 50 mg L−1. The half maximal effective concentration (EC50) values of compound 5g and 6g to V. mali were 1.21 and 1.90 mg L−1 respectively. The protective rate against apple canker of compound 5g reached 93.4% at 100 mg L−1 on twigs, superior to carbendazim (53.3%). When treated with 5g, the cell membrane permeability and leakage of content of V. mali increased, accompanied with the decrease of superoxide dismutase (SOD) and catalase (CAT) level. Concurrently, the mycelial hyphae contracted, wrinkled, and collapsed, providing evidence of membrane perturbation. A three‐dimensional quantitative structure–activity relationship (3D‐QSAR) between the topic compounds and the EC50 to V. mali was established showing good predictability (r2 = 0.971). CONCLUSION: Amphiphilic amidines can acquire antifungal activities by acting on the plasmic membrane. Compound 5g could be a promising lead in discovering novel fungicidal candidates. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Bacterial infections of the respiratory tract cause millions of deaths annually. Several diseases exist wherein (1) bacterial infection is the main cause of disease (e.g., tuberculosis and bacterial pneumonia), (2) bacterial infection is a consequence of disease and worsens the disease prognosis (e.g., cystic fibrosis), and (3) bacteria-triggered inflammation propagates the disease (e.g., chronic obstructive pulmonary disease). Current approaches to combat infections generally include long and aggressive antibiotic treatments, which challenge patient compliance, thereby making relapses common and contributing to the development of antibiotic resistance. Consequently, the proportion of infections that cannot be treated with conventional antibiotics is rapidly increasing, and novel therapies are urgently needed. In this context, antimicrobial peptides (AMPs) have received considerable attention as they may exhibit potent antimicrobial effects against antibiotic-resistant bacterial strains but with modest toxicity. In addition, some AMPs suppress inflammation and provide other host defense functions (motivating the alternative term host defense peptides (HDPs)). However, the delivery of AMPs is complicated because they are large, positively charged, and amphiphilic. As a result of this, AMP delivery systems have recently attracted attention. For airway infections, the currently investigated delivery approaches range from aerosols and dry powders to various self-assembly and nanoparticle carrier systems, as well as their combinations. In this paper, we discuss recent developments in the field, ranging from mechanistic mode-of-action studies to the application of these systems for combating bacterial infections in the airways. [ABSTRACT FROM AUTHOR]

The marine environment is the largest ecological habitat on Earth, albeit one of the least explored, particularly in terms of its microbial inhabitants. The marine fish gut is host to a diverse microbial community from which diverse bioactive molecules can be sourced. Due to the unique environmental pressures these microbial communities experience, the bioactive molecules they produce often evolve unique adaptations that give them diverse structures and activities, differentiating them from terrestrial homologues. Of particular interest, due to their structural and functional diversity, are the ribosomally-synthesized antimicrobial peptides (bacteriocins). With increasing pressure from emerging antibiotic-resistant disease and industrial demand for novel therapeutics, the marine fish gut microbiome represents a relatively untapped resource of novel bacteriocins that could prove beneficial to human health and aquaculture. This review presents an overview of the marine fish gut microbiome and explores its potential as a source of bacteriocins for human health with considerations for applications and future research in this area. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [R4W4] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [R4W4] against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) by a checkered board assay. [R4W4] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against E. coli (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [R4W4] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [R4W4] at a 16 mg/mL concentration stabilized the zeta potential of MRSA −31 ± 0.88 mV to −8.37 mV. Also, [R4W4] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [R4W4] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [R4W4] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [R4W4] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [R4W4] and a change in antibacterial effectiveness MIC [R4W4] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [R4W4] warrants further consideration as a potential AMP. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are the focus of this manuscript, as bioconservative molecules that constitute a major defense mechanism in many organisms. Various antimicrobial peptides have been isolated and identified, but AMPs derived from Hermetia illucens (HI) will be the focus of this review. The review focuses mainly on cecropins, defensins, and attacins. Hermetia illucens is a remarkable organism adapted to life in a diverse, often highly polluted environment, and its resilience is largely attributed to amps. Amps are active against many bacterial and fungal species and also act to induce the osmotic lysis of protozoa. They attack pathogenic microorganisms without damaging host cells in the process. Given the increasing antibiotic resistance of many bacterial strains in animal production, amps appear to be a tempting alternative as substances that limit and inhibit the growth and development of pathogens, as well as an option in veterinary medicine as potential substitutes for antibiotics, the administration of which must be limited in the european union. The amp content of HI larvae extracts, which determines their activity, depends on the larval diet and the solvent used. This review presents in vitro studies on the effects of amps from Hermetia illucens on microorganisms and in vivo studies on the potential of Hi larvae meal as a feed supplement. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a growing concern due to the growth of antibiotic-resistant microorganisms, which makes it difficult to treat infection. Due to its broad-spectrum antimicrobial properties against a diverse array of bacteria, both Gram-positive and Gram-negative bacteria, and fungi, Rhynchophorus ferrugineus larval antimicrobial peptides (AMPs) have demonstrated potential as antimicrobial agents for the treatment of microbial infections and prevention of antibiotic resistance. This study emphasizes the unexplored mechanisms of action of R. ferrugineus larvae against microorganisms. Among the most widely discussed mechanisms is the effect of AMPs in larvae in response to a threat or infection. Modulation of immune-related genes in the intestine and phagocytic capacity of its hemocytes may also affect the antimicrobial activity of R. ferrugineus larvae, with an increase in phenoloxidase activity possibly correlated with microbial clearance and survival rates of larvae. The safety and toxicity of R. ferrugineus larvae extracts, as well as their long-term efficacy, are also addressed in this paper. The implications of future research are explored in this paper, and it is certain that R. ferrugineus larvae have the potential to be developed as a broad-spectrum antimicrobial agent with proper investigation. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides have been developed based on plant-derived molecular scaffolds for the treatment of infectious diseases. Chenopodin is an abundant seed storage protein in quinoa, an Andean plant with high nutritional and therapeutic properties. Here, we used computer- and physicochemical-based strategies and designed four peptides derived from the primary structure of Chenopodin. Two peptides reproduce natural fragments of 14 amino acids from Chenopodin, named Chen1 and Chen2, and two engineered peptides of the same length were designed based on the Chen1 sequence. The two amino acids of Chen1 containing amide side chains were replaced by arginine (ChenR) or tryptophan (ChenW) to generate engineered cationic and hydrophobic peptides. The evaluation of these 14-mer peptides on Staphylococcus aureus and Escherichia coli showed that Chen1 does not have antibacterial activity up to 512 µM against these strains, while other peptides exhibited antibacterial effects at lower concentrations. The chemical substitutions of glutamine and asparagine by amino acids with cationic or aromatic side chains significantly favoured their antibacterial effects. These peptides did not show significant hemolytic activity. The fluorescence microscopy analysis highlighted the membranolytic nature of Chenopodin-derived peptides. Using molecular dynamic simulations, we found that a pore is formed when multiple peptides are assembled in the membrane. Whereas, some of them form secondary structures when interacting with the membrane, allowing water translocations during the simulations. Finally, Chen2 and ChenR significantly reduced SARS-CoV-2 infection. These findings demonstrate that Chenopodin is a highly useful template for the design, engineering, and manufacturing of non-toxic, antibacterial, and antiviral peptides. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a global concern, far from being resolved. The need of new drugs against new targets is imminent. In this work, we present a family of aminoalkyl resveratrol derivatives with antibacterial activity inspired by the properties of cationic amphipathic antimicrobial peptides. Surprisingly, the newly designed molecules display modest activity against aerobically growing bacteria but show surprisingly good antimicrobial activity against anaerobic bacteria (Gram-negative and Gram-positive) suggesting specificity towards this bacterial group. Preliminary studies into the action mechanism suggest that activity takes place at the membrane level, while no cross-resistance with traditional antibiotics is observed. Actually, some good synergistic relations with existing antibiotics were found against Gram-negative pathogens. However, some cytotoxicity was observed, despite their low haemolytic activity. Our results show the importance of the balance between positively charged moieties and hydrophobicity to improve antimicrobial activity, setting the stage for the design of new drugs based on these molecules. [ABSTRACT FROM AUTHOR]

The rise of drug-resistant bacteria is a major threat to public health, highlighting the urgent need for new antimicrobial compounds and treatments. Bacteriocins, which are ribosomally synthesized antimicrobial peptides produced by bacteria, hold promise as alternatives to conventional antibiotics. In this study, we identified and characterized a novel leaderless bacteriocin, bawcin, the first bacteriocin to be characterized from a Bacillus wiedmannii species. Chemically synthesized and purified bawcin was shown to be active against a broad range of Gram-positive bacteria, including foodborne pathogens Staphylococcus aureus, Bacillus cereus, and Listeria monocytogenes. Stability screening revealed that bawcin is stable over a wide range of pH (2.0–10.0), temperature conditions (25–100 °C), and against the proteases, papain and pepsin. Lastly, three-dimensional structure homology modeling suggests that bawcin contains a saposin-fold with amphipathic helices and a highly cationic surface that may be critical for membrane interaction and the subsequent cell death of its targets. This study provides the foundational understanding of the activity and properties of bawcin, offering valuable insights into its applications across different antimicrobial uses, including as a natural preservative in food and livestock industries. [ABSTRACT FROM AUTHOR]

The purpose of the study is to develop a novel peptide for caries management. Gallic-Acid-Polyphemusin-I (GAPI) was synthesised by grafting Polyphemusin I (PI) and gallic acid (GA). Biocompatibility was evaluated using a Cell Counting Kit-8 Assay. Antimicrobial properties were assessed using minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). The bacterial and fungal morphology after GAPI treatment was investigated using transmission electron microscopy (TEM). The architecture of a consortium biofilm consisting of Streptococcus mutans, Lacticaseibacillus casei and Candida albicans was evaluated using scanning electron microscopy (SEM) and confocal laser scanning microscopy. The growth kinetics of the biofilm was examined using a propidium monoazide–quantitative polymerase chain reaction. The surface and calcium-to-phosphorus molar ratio of GAPI-treated enamel after pH cycling were examined with SEM and energy-dispersive X-ray spectroscopy. Enamel crystal characteristics were analysed using X-ray diffraction. Lesion depths representing the enamel's mineral loss were assessed using micro-computed tomography. The MIC of GAPI against S. mutans, L. casei and C. albicans were 40 μM, 40 μM and 20 μM, respectively. GAPI destroyed the biofilm's three-dimensional structure and inhibited the growth of the biofilm. SEM showed that enamel treated with GAPI had a relatively smooth surface compared to that treated with water. The calcium-to-phosphorus molar ratio of enamel treated with GAPI was higher than that of the control. The lesion depths and mineral loss of the GAPI-treated enamel were less than the control. The crystallinity of the GAPI-treated enamel was higher than the control. This study developed a biocompatible, mineralising and antimicrobial peptide GAPI, which may have potential as an anti-caries agent. [ABSTRACT FROM AUTHOR]

With the increase in drug-resistant bacteria, new antibacterial drugs have emerged as a prominent area of research and development. Antimicrobial peptides (AMPs), as innate immune agents, have garnered significant attention due to their potent, rapid, and broad-spectrum antibacterial activity. This study focused on investigating the functionality of three AMPs (CATH 1, CATH 2, and MAP34-B) derived from goat submandibular glands. Among these AMPs, CATH 2 and MAP34-B exhibited direct antibacterial activity against both Gram-negative and Gram-positive bacteria, primarily targeting the bacterial membrane. Additionally, these two AMPs were found to have the potential to induce reactive oxygen species (ROS) production in bacterial cells and interact with bacterial genome DNA, which may play a crucial role in their mechanisms of action. Furthermore, both CATH 1 and CATH 2 demonstrated significant antioxidant activity, and all three AMPs exhibited potential anti-inflammatory activity. Importantly, the cytotoxic activity of these AMPs against mammalian cells was found to be weak, and their hemolytic activity was extremely low. Overall, the characteristics of these three AMPs found in goat submandibular glands offer new insights for the study of host protection from an immunological perspective. They hold promise as potential candidates for the development of novel antibacterial agents, particularly in the context of combating drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Lactiplantibacillus plantarum (L. plantarum) produces an antimicrobial peptide known as plantaricin. Plantaricin-producing L. plantarum is of interest for its gut-friendly nature, wide range of sugar utilization, palatability, and probiotic attributes, making it a better candidate for the food industry. Numerous strains of plantaricin-producing L. plantarum have been isolated from different ecological niches and found to follow different mechanisms for plantaricin production. The mechanism of plantaricin production is sensitive to environmental factors; therefore, any alteration in the optimum conditions can inhibit/halt bacteriocin production. To regain the lost or hidden plantaricin-producing character of the L. plantarum strains under ideal laboratory conditions, it is essential to understand the mechanism of plantaricin production. Previously, discrete information on various mechanisms of plantaricin production has been elaborated. However, based on the literature analysis, we observed that a systematic classification of plantaricins produced by L. plantarum is not explored. Hence, we aim to collect information about rapidly emerging plantaricins and distribute them among the different classes of bacteriocin, followed by classifying them based on different mechanisms of plantaricin production. This may help scaleup the bacteriocin production at industrial levels, which is otherwise challenging to achieve. This will also help the reader understand plantaricins and their mechanism of plantaricin production to a deeper extent and to characterize/reproduce the peptide where plantaricin production is a hidden character. Key points: • L. plantarum produces the antimicrobial compound plantaricin. • L. plantarum has different regulatory operons which control plantaricin production. • Based on the regulatory operon, the mechanism of plantaricin production is different. [ABSTRACT FROM AUTHOR]

The discovery of new antimicrobials is necessary to combat multidrug-resistant (MDR) bacteria, especially those that infect wounds and form prodigious biofilms, such as Acinetobacter baumannii. Antimicrobial peptides (AMPs) are a promising class of new therapeutics against drug-resistant bacteria, including gram-negatives. Here, we utilized a computational AMP design strategy combining database filtering technology plus positional analysis to design a series of novel peptides, named HRZN, designed to be active against A. baumannii. All of the HRZN peptides we synthesized exhibited antimicrobial activity against three MDR A. baumannii strains with HRZN-15 being the most active (MIC 4 µg/mL). This peptide also inhibited and eradicated biofilm of A. baumannii strain AB5075 at 8 and 16 µg/mL, which is highly effective. HRZN-15 permeabilized and depolarized the membrane of AB5075 rapidly, as demonstrated by the killing kinetics. HRZN 13 and 14 peptides had little to no hemolysis activity against human red blood cells, whereas HRZN-15, -16, and -17 peptides demonstrated more significant hemolytic activity. HRZN-15 also demonstrated toxicity to waxworms. Further modification of HRZN-15 could result in a new peptide with an improved toxicity profile. Overall, we successfully designed a set of new AMPs that demonstrated activity against MDR A. baumannii using a computational approach. [ABSTRACT FROM AUTHOR]

A novel antimicrobial peptide, GAPI, has been developed recently by grafting gallic acid (GA) to polyphemusin I (PI). The objective of this study was to investigate the antibacterial effects of GAPI on common oral pathogens. This laboratory study used minimum inhibitory concentrations and minimum bactericidal concentrations to assess the antimicrobial properties of GAPI against common oral pathogens. Transmission electron microscopy was used to examine the bacterial morphology both before and after GAPI treatment. The results showed that the minimum inhibitory concentration ranged from 20 μM (Lactobacillus rhamnosus) to 320 μM (Porphyromonas gingivalis), whereas the minimum bactericidal concentration ranged from 80 μM (Lactobacillus acidophilus) to 640 μM (Actinomyces naeslundii, Enterococcus faecalis, and Porphyromonas gingivalis). Transmission electron microscopy showed abnormal curvature of cell membranes, irregular cell shapes, leakage of cytoplasmic content, and disruption of cytoplasmic membranes and cell walls. In conclusion, the GAPI antimicrobial peptide is antibacterial to common oral pathogens, with the potential to be used to manage oral infections. [ABSTRACT FROM AUTHOR]

The use of antibiotics for the control of infections has not only been banned by FDA for use in food-producing animals, but also several countries have prohibited their use in aquaculture because of several reasons such as the occurrence of antibiotic-tolerant microorganisms, accumulation of antibiotic residues in fish and shrimp flesh, and aquatic environmental effluence concerns. These issues have led researchers and aquaculture scientists to conduct several studies to find antibiotic alternatives. Numerous substitutes have been evaluated, such as probiotics, synbiotics, prebiotics, postbiotics, phytogenics, essential oils, and several others. Results show that these supplements demonstrate proven efficacy in enhancing immune responses, reducing mortalities resulting from experimental infections, and reducing antibiotic usage in medicated aquafeed. Nonetheless, using antimicrobial peptides (AMPs) to control fish diseases and as antibiotic alternatives is a promising and interesting research topic. AMPs are a vital class of small peptides that could stimulate the innate immune system against challenging pathogens and also possess significant potent defensive responses against a variety of infectious and noninfectious pathogenic agents, including bacteria, parasites, fungi, and viruses. Regarding their source origin, AMPs can be classified into six main types: mammalian-, amphibian-, insect-, aquatic-, plant-, and microorganism-derived AMPs. On account of their unique structure, they can display an essential function in therapeutic strategies against infectious diseases affecting fish and shrimp. Reports showed several kinds of AMPs had a wide spectrum of antimicrobial properties. These effects are besides their prominent immunostimulatory functions. Thus, they may be considered a functional alternative to antibiotics in aquaculture. This article provides information on the current knowledge about the modes of action, sources, classification, functions, and potential applications for the development of aquatic animal health. The information included in this context will be valuable to enhance the sustainability of aquaculture. [ABSTRACT FROM AUTHOR]

A material with the ability to rapidly eradicate bacteria via a contact-killing mechanism has the benefit of a more localised treatment that is easy to implement when needed to prevent or treat a bacterial infection. Here, we present an antimicrobial material based on covalently attached antimicrobial peptides (AMPs) to a soft amphiphilic hydrogel. This results in a material that exhibits an antimicrobial effect based on contact-killing. In this study, the antimicrobial efficacy of the AMP-hydrogel was investigated by observing the changes in total bioburden on the intact skin of healthy human volunteers when the AMP-hydrogel dressing was placed on the forearm for three hours. The AMP-hydrogel significantly reduced the bioburden on the skin from a mean value of 1200CFU/cm2 for the untreated skin to 23CFU/cm2. Biocompatibility evaluations of the AMP-hydrogel showed no sign of cytotoxicity, acute systemic toxicity, irritation or sensitisation, demonstrating the safety of the AMP-hydrogel as a potential wound dressing. Leachability studies confirmed no release of AMPs and that the antimicrobial effect was localised to the surface of the hydrogels, demonstrating a pure contact-killing mode of action. [ABSTRACT FROM AUTHOR]

Currently, it is crucial to screen efficient, safe, and accessible therapies from a variety of prospective antimicrobial agents due to the rapid development of microbial resistance against chemotherapeutic drugs (mainly antibiotics). Bacteriocins are a type of antimicrobial peptide created by bacteria that are ribosomally synthesized. Bacteriocins have evolved into one of the tools used to combat bacteria because of their distinctive traits. Therefore, bacteriocins may replace antibiotics to treat multiple drugs resistance pathogens. Accordingly, the purpose of this study was to investigate the antibacterial effects of secondary metabolites from two bacteriocinproducing strains (Lactobacillus acidophilus (LA102) and Lacticaseibacillus casei (LC232)) on 24 pathogenic and spoilage microorganisms either alone or in combination. The 50% inhibitory concentration, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), or minimum fungicidal concentration (MFC) were determined. The fractional inhibitory concentration (FIC) and its effect were also defined. Results showed that all the 12 bacterial and ten fungal strains were inhibited by both bacteriocin-producing strains and only four fungal strains were not affected by all studied 12 strains. It was found that the bactericidal activity of both bacteriocin-producing strains against S. aureus, L. monocytogenes, and the fungi strains M. phaseolina was the highest among all the tested strains. It was also noticed that a combination of (LA102) and (LC232) gives a 20% synergistic effect and 40 % additive relationship and indifferent relationship without any microbes showing an antagonistic relationship. Moreover, to screen for better functional and bacteriocin-producing strains, this study offers a practical, thorough, and shared profile of newly developed antimicrobial agents. [ABSTRACT FROM AUTHOR]

Aquaculture production is at a record level and is estimated to increase in the coming years. However, this production can be negatively affected by infectious diseases produced by viruses, bacteria, and parasites, causing fish mortality and economic losses. Antimicrobial peptides (AMPs) are small peptides that may be promising candidates to replace antibiotics because they are the first line of defense in animals against a wide variety of pathogens and have no negative effects; they also show additional activities such as antioxidant or immunoregulatory functions, which makes them powerful alternatives for use in aquaculture. Moreover, AMPs are highly available in natural sources and have already been used in the livestock farming and food industries. Photosynthetic marine organisms can survive under all kinds of environmental conditions and under extremely competitive environments thanks to their flexible metabolism. For this reason, these organisms represent a powerful source of bioactive molecules as nutraceuticals and pharmaceuticals, including AMPs. Therefore, in this study we reviewed the present knowledge about AMPs from photosynthetic marine organism sources and analyzed whether they could be suitable for use in aquaculture. [ABSTRACT FROM AUTHOR]

The efficient preparation of novel bioactive peptide drugs requires the availability of reliable and accessible chemical methodologies together with suitable analytical techniques for the full characterisation of the synthesised compounds. Herein, we describe a novel acidolytic method with application to the synthesis of cyclic and linear peptides involving benzyl-type protection. The process consists of the in situ generation of anhydrous hydrogen bromide and a trialkylsilyl bromide that acts as protic and Lewis acid reagents. This method proved to be useful to effectively remove benzyl-type protecting groups and cleave Fmoc/tBu assembled peptides directly attached to 4-methylbenzhydrylamine (MBHA) resins with no need for using mild trifluoroacetic acid labile linkers. The novel methodology was successful in synthesising three antimicrobial peptides, including the cyclic compound polymyxin B3, dusquetide, and RR4 heptapeptide. Furthermore, electrospray mass spectrometry (ESI-MS) is successfully used for the full characterisation of both the molecular and ionic composition of the synthetic peptides. [ABSTRACT FROM AUTHOR]

Antibiotic resistance has exponentially increased during the last years. It is necessary to develop new antimicrobial drugs to prevent and treat infectious diseases caused by multidrug- or extensively-drug resistant (MDR/XDR)-bacteria. Host Defense Peptides (HDPs) have a versatile role, acting as antimicrobial peptides and regulators of several innate immunity functions. The results shown by previous studies using synthetic HDPs are only the tip of the iceberg, since the synergistic potential of HDPs and their production as recombinant proteins are fields practically unexplored. The present study aims to move a step forward through the development of a new generation of tailored antimicrobials, using a rational design of recombinant multidomain proteins based on HDPs. This strategy is based on a two-phase process, starting with the construction of the first generation molecules using single HDPs and further selecting those HDPs with higher bactericidal efficiencies to be combined in the second generation of broad-spectrum antimicrobials. As a proof of concept, we have designed three new antimicrobials, named D5L37βD3, D5L37D5L37 and D5LAL37βD3. After an in-depth exploration, we found D5L37D5L37 to be the most promising one, since it was equally effective against four relevant pathogens in healthcare-associated infections, such as methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis (MRSE) and MDR Pseudomonas aeruginosa, being MRSA, MRSE and P. aeruginosa MDR strains. The low MIC values and versatile activity against planktonic and biofilm forms reinforce the use of this platform to isolate and produce unlimited HDP combinations as new antimicrobial drugs by effective means. [ABSTRACT FROM AUTHOR]

The scenario of growing microbial resistance and of lack of interest of pharmaceutical companies in developing new antimicrobial drugs jeopardizes the present and the future of the treatment of infectious diseases. Different approaches such as antimicrobial peptides and CRISP-R have been explored to manage this situation, however, they have important limitations such as their high cost. Natural products comprise complex molecular structures for which reports of bacterial resistance are rare. They present specific and/or unspecific mechanisms of action that can be explored to provide safe and effective management of infectious diseases. In this review we assessed phytoextracts with evidence of their benefits for treating infectious diseases in humans and animals, towards the use of data for clinical and experimental purposes. Mechanisms of bacterial resistance to antimicrobials are also discussed. [ABSTRACT FROM AUTHOR]

Gomesin is a cationic antimicrobial peptide which is isolated from the haemocytes of the Brazilian tarantula Acanthoscurria gomesiana and can be produced chemically by Fmoc solid-phase peptide synthesis. Gomesin exhibits a range of biological activities, as demonstrated by its toxicity against therapeutically relevant pathogens such as Gram-positive or Gram-negative bacteria, fungi, cancer cells, and parasites. In recent years, a cyclic version of gomesin has been used for drug design and development as it is more stable than native gomesin in human serum and can penetrate and enter cancer cells. It can therefore interact with intracellular targets and has the potential to be developed as a drug lead for to treat cancer, infectious diseases, and other human diseases. This review provides a perspective on the discovery, structure–activity relationships, mechanism of action, biological activity, and potential clinical applications of gomesin. [ABSTRACT FROM AUTHOR]

Temporins are short peptides secreted by frogs from all over the world. They exert antimicrobial activity, mainly against Gram-positive bacteria, including resistant pathogens; recent studies highlight other possible applications of these peptides as anticancer or antiviral agents. This review is meant to describe the main features of temporins produced by different ranid genera. Due to the abundance of published papers, we focus on the most widely investigated peptides. We report studies on their mechanism of action and three-dimensional structure in model systems mimicking bacterial membranes or in the presence of cells. The design and the antimicrobial activity of peptide analogues is also described, with the aim of highlighting elements that are crucial to improve the bioactivity of peptides while reducing their toxicity. Finally, a short section is dedicated to the studies aimed at applying these peptides as drugs, to produce new antimicrobial materials or in other technological uses. [ABSTRACT FROM AUTHOR]

Microalgae are photosynthetic cell factories that produce a spectrum of bioactive compounds extensively used for various applications. Owing to the increase in antibiotic resistance among microbial pathogens, there is a significant thrust for identifying new treatment strategies, and antimicrobial peptides (AMPs) generation is one such method. These AMPs have multiple roles and are active against bacteria, fungi, and viruses. Such peptides synthesized in microalgae have a significant role in medical application, managing aquaculture‐associated diseases, and the food industry. To increase their effectiveness and novel peptides, genetically modified microalgae are used as cell factories. With the advancement of new technologies like the CRISPR‐Cas system, new avenues are opened for developing novel AMPs using microalgae. This review gives us insight into the various AMPs produced by microalgae and multiple technologies involved in creating such therapeutically essential molecules. Significance statement: Antimicrobial peptides (AMPs) are widely studied. However, this present manuscript mainly focuses on AMPs from microalgae. This also tries to shed light on the research gaps and the major challenges in microalgae‐derived AMPs. The technological advancements in AMPs production and its progress also have been addressed. [ABSTRACT FROM AUTHOR]

Aim This study was aimed to determine antimicrobial and antiviral activity of a novel lanthipeptide from a Brevibacillus sp. for disinfectant application. Methods and results The antimicrobial peptide (AMP) was produced by a bacterial strain AF8 identified as a member of the genus Brevibacillus representing a novel species. Whole genome sequence analysis using BAGEL identified a putative complete biosynthetic gene cluster involved in lanthipeptide synthesis. The deduced amino acid sequence of lanthipeptide named as brevicillin, showed >30% similarity with epidermin. Mass determined by MALDI-MS and Q-TOF suggested posttranslational modifications like dehydration of all Ser and Thr amino acids to yield Dha and Dhb, respectively. Amino acid composition determined upon acid hydrolysis is in agreement with core peptide sequence deduced from the putative biosynthetic gene bvrAF8. Biochemical evidence along with stability features ascertained posttranslational modifications during formation of the core peptide. The peptide showed strong activity with 99% killing of pathogens at 12 μg ml−1 within 1 minute. Interestingly, it also showed potent anti-SARS-CoV-2 activity by inhibiting ∼99% virus growth at 10 μg ml−1 in cell culture-based assay. Brevicillin did not show dermal allergic reactions in BALB/c mice. Conclusion This study provides detailed description of a novel lanthipeptide and demonstrates its effective antibacterial, antifungal and anti-SARS-CoV-2 activity. [ABSTRACT FROM AUTHOR]

Background: SAAP-148 is an antimicrobial peptide derived from LL-37. It exhibits excellent activity against drug-resistant bacteria and biofilms while resisting degradation in physiological conditions. Despite its optimal pharmacological properties, its mechanism of action at the molecular level has not been explored. Methods: The structural properties of SAAP-148 and its interaction with phospholipid membranes mimicking mammalian and bacterial cells were studied using liquid and solid-state NMR spectroscopy as well as molecular dynamics simulations. Results: SAAP-148 is partially structured in solution and stabilizes its helical conformation when interacting with DPC micelles. The orientation of the helix within the micelles was defined by paramagnetic relaxation enhancements and found similar to that obtained using solid-state NMR, where the tilt and pitch angles were determined based on 15N chemical shift in oriented models of bacterial membranes (POPE/POPG). Molecular dynamic simulations revealed that SAAP-148 approaches the bacterial membrane by forming salt bridges between lysine and arginine residues and lipid phosphate groups while interacting minimally with mammalian models containing POPC and cholesterol. Conclusions: SAAP-148 stabilizes its helical fold onto bacterial-like membranes, placing its helix axis almost perpendicular to the surface normal, thus probably acting by a carpet-like mechanism on the bacterial membrane rather than forming well-defined pores. [ABSTRACT FROM AUTHOR]

Researchers have developed novel bioactive materials for caries management. Many clinicians also favour these materials, which fit their contemporary practice philosophy of using the medical model of caries management and minimally invasive dentistry. Although there is no consensus on the definition of bioactive materials, bioactive materials in cariology are generally considered to be those that can form hydroxyapatite crystals on the tooth surface. Common bioactive materials include fluoride-based materials, calcium- and phosphate-based materials, graphene-based materials, metal and metal-oxide nanomaterials and peptide-based materials. Silver diamine fluoride (SDF) is a fluoride-based material containing silver; silver is antibacterial and fluoride promotes remineralisation. Casein phosphopeptide-amorphous calcium phosphate is a calcium- and phosphate-based material that can be added to toothpaste and chewing gum for caries prevention. Researchers use graphene-based materials and metal or metal-oxide nanomaterials as anticaries agents. Graphene-based materials, such as graphene oxide-silver, have antibacterial and mineralising properties. Metal and metal-oxide nanomaterials, such as silver and copper oxide, are antimicrobial. Incorporating mineralising materials could introduce remineralising properties to metallic nanoparticles. Researchers have also developed antimicrobial peptides with mineralising properties for caries prevention. The purpose of this literature review is to provide an overview of current bioactive materials for caries management. [ABSTRACT FROM AUTHOR]

The objective of this study was to review the design methods that have been used to create peptides for use in caries management. Two independent researchers systematically reviewed many in vitro studies in which peptides were designed for use in caries management. They assessed the risk of bias in the included studies. This review identified 3592 publications, of which 62 were selected. Forty-seven studies reported 57 antimicrobial peptides. Among them, 31 studies (66%, 31/47) used the template-based design method; 9 studies (19%, 9/47) used the conjugation method; and 7 studies (15%, 7/47) used other methods, such as the synthetic combinatorial technology method, the de novo design method and cyclisation. Ten studies reported mineralising peptides. Seven of these (70%, 7/10) used the template-based design method, two (20%, 2/10) used the de novo design method, and one study (10%, 1/10) used the conjugation method. In addition, five studies developed their own peptides with antimicrobial and mineralising properties. These studies used the conjugation method. Our assessment for the risk of bias in the 62 reviewed studies showed that 44 publications (71%, 44/62) had a medium risk and that 3 publications had a low risk (5%, 3/62). The two most common methods for developing peptides for use in caries management that were used in these studies were the template-based design method and the conjugation method. [ABSTRACT FROM AUTHOR]

In the past decade, there has been fast-growing interest among researchers to discover bioactive peptides from edible insects and to evaluate their potential applications in the management of human, livestock, and plant health. This review summarizes current knowledge of insect-derived peptides and their potential role in tackling human health issues and solving agriculture problems by protecting crops and livestock against their pathogens. Numerous bioactive peptides have been identified from edible insect species, including peptides that were enzymatically liberated from insect proteins and endogenous peptides that occur naturally in insects. The peptides exhibited diverse bioactivities, encompassing antioxidant, anti-angiotensin-converting enzyme, anti-dipeptidyl peptidase-IV, anti-glucosidase, anti-lipase, anti-lipoxygenase, anti-cyclooxygenase, anti-obesity, and hepatoprotective activities. Such findings point to their potential contribution to solving human health problems related to inflammation, free radical damage, diabetes, hypertension, and liver damage, among others. Although most of the experiments were performed in vitro, evidence for the in vivo efficacy of some peptides is emerging. Evidence of the protective effects of insect-derived endogenous antimicrobial peptides in combating farm animal and plant pathogens is available. The ability of insect-derived endogenous neuropeptides to protect plants against herbivorous insects has been demonstrated as well. Nevertheless, the potency of peptides identified from insect protein hydrolysates in modulating livestock and plant health remains a knowledge gap to be filled. [ABSTRACT FROM AUTHOR]

The scenario of growing microbial resistance and of lack of interest of pharmaceutical companies in developing new antimicrobial drugs jeopardizes the present and the future of the treatment of infectious diseases. Different approaches such as antimicrobial peptides and CRISP-R have been explored to manage this situation, however, they have important limitations such as their high cost. Natural products comprise complex molecular structures for which reports of bacterial resistance are rare. They present specific and/or unspecific mechanisms of action that can be explored to provide safe and effective management of infectious diseases. In this review we assessed phytoextracts with evidence of their benefits for treating infectious diseases in humans and animals, towards the use of data for clinical and experimental purposes. Mechanisms of bacterial resistance to antimicrobials are also discussed. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is associated with repeated lung bacterial infection, mainly by Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium abscessus, all known to be or becoming resistant to several antibiotics, often leading to therapeutic failure and death. In this context, antimicrobial peptides and antimicrobial polymers active against resistant strains and less prompt to cause resistance, appear as a good alternative to conventional antibiotics. In the present study, methacrylate-based copolymers obtained by radical chemistry were evaluated against CF-associated bacterial strains. Results showed that the type (Random versus Diblock) and the size of the copolymers affected their antibacterial activity and toxicity. Among the different copolymers tested, four (i.e., Random10200, Random15000, Random23900, and Diblock9500) were identified as the most active and the safest molecules and were further investigated. Data showed that they inserted into bacterial lipids, leading to a rapid membranolytic effect and killing of the bacterial. In relation with their fast bactericidal action and conversely to conventional antibiotics, those copolymers did not induce a resistance and remained active against antibiotic-resistant strains. Finally, the selected copolymers possessed a preventive effect on biofilm formation, although not exhibiting disruptive activity. Overall, the present study demonstrates that methacrylate-based copolymers are an interesting alternative to conventional antibiotics in the treatment of CF-associated bacterial infection. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is considered the oldest pandemic in human history. The emergence of multidrug-resistant (MDR) strains is currently considered a serious global health problem. As components of the innate immune response, antimicrobial peptides (AMPs) such as cathelicidins have been proposed to have efficacious antimicrobial activity against Mycobacterium tuberculosis (Mtb). In this work, we assessed a cathelicidin from water buffalo, Bubalus bubalis, (WBCATH), determining in vitro its antitubercular activity (MIC), cytotoxicity and the peptide effect on bacillary loads and cytokines production in infected alveolar macrophages. Our results showed that WBCATH has microbicidal activity against drug-sensitive and MDR Mtb, induces structural mycobacterial damage demonstrated by electron microscopy, improves Mtb killing and induces the production of protective cytokines by murine macrophages. Furthermore, in vivo WBCATH showed decreased bacterial loads in a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive or MDR mycobacteria. In addition, a synergistic therapeutic effect was observed when first-line antibiotics were administered with WBCATH. These results were supported by computational modeling of the potential effects of WBCATH on the cellular membrane of Mtb. Thus, this water buffalo-derived cathelicidin could be a promising adjuvant therapy for current anti-TB drugs by enhancing a protective immune response and potentially reducing antibiotic treatment duration. [ABSTRACT FROM AUTHOR]

Objective: Researchers are studying the use of antimicrobial peptides as functional biomaterials to prevent and treat dental caries. This study aims to investigate the global research interest in antimicrobial peptides for caries management. Methods: Two independent investigators systematically searched with keywords ('Caries' OR 'Dental caries') AND ('Antimicrobial peptide' OR 'AMP' OR 'Statherin' OR 'Histatin' OR 'Defensin' OR 'Cathelicidin') on Web of Science, PubMed and Scopus. They removed duplicate publications and screened the titles and abstracts to identify relevant publications. The included publications were summarized and classified as laboratory studies, clinical trials or reviews. The citation count and citation density of the three publication types were compared using a one-way analysis of variance. The publications' bibliometric data were analyzed using the Bibliometrix program. Results: This study included 163 publications with 115 laboratory studies (71%), 29 clinical trials (18%) and 19 reviews (11%). The number of publications per year have increased steadily since 2002. The citation densities (mean ± SD) of laboratory study publications (3.67 ± 2.73) and clinical trial publications (2.63 ± 1.85) were less than that of review articles (5.79 ± 1.27) (p = 0.002). The three publication types had no significant difference in citation count (p = 0.54). Most publications (79%, 129/163) reported the development of a novel antimicrobial peptide. China (52/163, 32%) and the US (29/163, 18%) contributed to 50% (81/163) of the publications. Conclusion: This bibliometric analysis identified an increasing trend in global interest in antimicrobial peptides for caries management since 2002. The main research topic was the development of novel antimicrobial peptides. Most publications were laboratory studies, as were the three publications with the highest citation counts. Laboratory studies had high citation counts, whereas reviews had high citation density. [ABSTRACT FROM AUTHOR]

[Display omitted] • New Homo branched and Hetero branched analogues of the battacin peptide were synthesized and characterized. • Branching improved the antibacterial activity of the peptides in the presence and absence of physiological salt conditions by 10 fold. • Antibiofilm activity of the dibranched peptide showed > 85 % eradication of preformed MRSA and A.baumannii biofilms at low micromolar concentration. • Cytotoxicity profile of the peptides was determined using mouse red blood cells and human dermal fibroblast cell lines. Di-branched and tetra-branched versions of a previously reported analogue of the lipopeptide battacin were successfully synthesised using thiol-maleimide click and 1, 2, 3-triazole click chemistry. Antimicrobial studies against drug resistant clinical isolates of Escherichia coli (ESBL E. coli Ctx-M14), Pseudomonas aeruginosa (P. aeruginosa Q502), and Methicillin resistant Staphylococcus aureus (MRSA ATCC 33593), as well as clinically isolated Acinetobacter baumannii (A. baumannii ATCC 19606), and P. aeruginosa (ATCC 27853), revealed that the dendrimeric peptides have antimicrobial activity in the low micromolar range (0.5 –– 4 μM) which was 10 times more potent than the monomer peptides. Under high salt concentrations (150 mM NaCl, 2 mM MgCl 2 , and 2.5 mM CaCl 2) the di-branched lipopeptides retained their antimicrobial activity while the monomer peptides were not active (>100 μM). The di-branched triazole click lipopeptide, Peptide 12 , was membrane lytic, showed faster killing kinetics, and exhibited antibiofilm activity against A. baumannii and MRSA and eradicated > 85 % preformed biofilms at low micromolar concentrations. The di-branched analogues were > 30-fold potent than the monomers against Candida albicans. Peptide 12 was not haemolytic (HC10 = 932.12 μM) and showed up to 40-fold higher selectivity against bacteria and fungi than the monomer peptide. Peptide 12 exhibited strong proteolytic stability (>80 % not degraded) in rat serum over 24 h whereas > 95 % of the thiol-maleimide analogue (Peptide 10) was degraded. The tetra-branched peptides showed comparable antibacterial potency to the di-branched analogues. These findings indicate that dual branching using triazole click chemistry is a promising strategy to improve the antimicrobial activity and proteolytic stability of battacin based lipopeptides. The information gathered can be used to build effective antimicrobial dendrimeric peptides as new peptide antibiotics. [ABSTRACT FROM AUTHOR]

Background: Tau is an established substrate for gingipains secreted by Porphyromonas gingivalis. Hyperphosphorylation of tau and neurofibrillary tangle (NFT) formation is a defining lesion of Alzheimer's disease (AD) where NFT distribution is related to Braak stage and disease severity.Objective: To assess gingipains'-fragmented tau peptides for their antimicrobial properties and for the likelihood of paired helical/straight filament (PHF/SF) formation with implications for the NFT lesion.Methods: Seven non-phosphorylated (A-G) and three phosphorylated (A-C) tau peptides, were tested for antimicrobial properties against P. gingivalis. Polarizing light properties were determined using Congo Red staining. Secondary and tertiary structures of peptides B-F were determined using transmission electron microscopy (TEM) and circular dichroism (CD) was undertaken for the soluble peptides A in phosphorylated and non-phosphorylated states.Results: Phosphorylated tau peptide A displayed a significant effect against planktonic P. gingivalis. The CD results demonstrated that both peptides A, in phosphorylated and non-phosphorylated states, in aqueous solution, adopted mainly β-type structures. Non-phosphorylated peptides B-F and phosphorylated peptides B-C were insoluble and fibrillar under the TEM. The secondary and tertiary structures of the non-phosphorylated peptide B demonstrated fewer helical twists, whereas peptide C displayed significantly more helical twists along the whole fiber(s) length following its phosphorylation.Conclusion: Phosphorylated peptide A reduced P. gingivalis viability. CD spectroscopy demonstrated the phosphorylated and the non-phosphorylated peptide A predominantly formed from β-sheet structures in aqueous solution with potential antimicrobial activity. Phosphorylation of tau peptides physically changed their tertiary structure into PHFs with potential for self-aggregation and binding to the NFT lesion. [ABSTRACT FROM AUTHOR]

This review examines the role of reactive species RS (of oxygen ROS, nitrogen RNS and halogen RHS) on innate immunity. The importance of these species in innate immunity was first recognized in phagocytes that underwent a "respiratory burst" after activation. The anion superoxide •O2− and hydrogen peroxide H2O2 are detrimental to the microbial population. NADPH oxidase NOx, as an •O2− producer is essential for microbial destruction, and patients lacking this functional oxidase are more susceptible to microbial infections. Reactive nitrogen species RNS (the most important are nitric oxide radical -•NO, peroxynitrite ONOO— and its derivatives), are also harmful to microorganisms, including bacteria, viruses, and parasites. Hypochlorous acid HOCl and hypothiocyanous acid HOSCN synthesized through the enzyme myeloperoxidase MPO, which catalyzes the reaction between H2O2 and Cl− or SCN−, are important inorganic bactericidal molecules, effective against a wide range of microbes. This review also discusses the role of antimicrobial peptides AMPs and their induction of ROS. In summary, reactive species RS are the heart of the innate immune system, and they are necessary for microbial lysis in infections that can affect mammals throughout their lives. [ABSTRACT FROM AUTHOR]

Acyldepsipeptides (ADEPs) are a new class of emerging antimicrobial peptides (AMPs), which are currently explored for treatment of pathogenic infections, including tuberculosis (TB). These cyclic hydrophobic peptides have a unique bacterial target to the conventional anti-TB drugs, and present a therapeutic window to overcome Mycobacterium Tuberculosis (M. tb) drug resistance. ADEPs exerts their antibacterial activity on M. tb strains through activation of the protein homeostatic regulatory protease, the caseinolytic protease (ClpP1P2). ClpP1P2 is normally regulated and activated by the ClpP-ATPases to degrade misfolded and toxic peptides and/or short proteins. ADEPs bind and dysregulate all the homeostatic capabilities of ClpP1P2 while inducing non-selective proteolysis. The uncontrolled proteolysis leads to M. tb cell death within the host. ADEPs analogues that have been tested possess cytotoxicity and poor pharmacokinetic and pharmacodynamic properties. However, these can be improved by drug design techniques. Moreover, the use of nanomaterial in conjunction with ADEPs would yield effective synergistic effect. This new mode of action has potential to combat and eradicate the extensive multi-drug resistance (MDR) problem that is currently faced by the public health pertaining bacterial infections, especially TB. [ABSTRACT FROM AUTHOR]

The antimicrobial and immunomodulatory capacities of the peptide Css54 and the chemokine MCP-1 were tested. The first, a peptide isolated from the venom of the scorpion Centruroides suffusus suffusus was synthesized chemically. In contrast, the second is a monocyte chemoattractant expressed as a recombinant protein in our lab. It was observed in vitro that Css54 inhibited the growth of Salmonella enterica serovar Typhimurium (6.2 µg/mL). At high concentrations, it was toxic to macrophages (25 µg/mL), activated macrophage phagocytosis (1.5 µg/mL), and bound Salmonella LPS (3 µg/mL). On the other hand, the recombinant MCP-1 neither inhibited the growth of Salmonella Typhimurium nor was it toxic to macrophages (up to 25 µg/mL), nor activated macrophage phagocytosis or bound Salmonella LPS (up to 3 µg/mL). Although it was observed in vivo in mice Balb/C that both Css54 and MCP-1 did not resolve the intraperitoneal infection by S. Typhimurium, Css54 decreased the expression of IL-6 and increased IL-10, IL-12p70, and TNF-α levels; meanwhile, MCP-1 decreased the expression of IFN-γ and increased IL-12p70 and TNF-α. It was also observed that the combination of both molecules Css54 and MCP-1 increased the expression of IL-10 and TNF-α. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are diverse molecules that include powerful medications such as bacitracin and vancomycin, as well as potent bacterial signaling molecules. Several antimicrobial peptides elicit cell death in gram-positive species by binding to lipid II cycle intermediates and inhibiting the synthesis of peptidoglycan. Many gram-positive organisms have evolved an elegant mechanism to sense and resist such antimicrobial peptides. In these organisms, a "Bce-type" adenosine triphosphate-binding cassette (ABC) transporter forms a protein complex with a two-component system, and together these components sense and provide resistance to antimicrobial peptides present at the cell surface. Conformational switching of Bce-type transporters is proposed to be the stimulus that activates the associated two-component system through a novel flux-sensing mechanism. In this work, we determined the detergent-solubilized structure of the Bcetype ABC transporter BceAB from Bacillus subtilis in two distinct conformational states using cryo-electron microscopy. Together with mass spectrometry and enzymatic data, our structures reveal the overall architecture of the Bce-type transporter family, uncover a specialized lipid-binding pocket for lipid II cycle intermediates, and reveal the conformational changes that are proposed to initiate signaling through the associated twocomponent system. [ABSTRACT FROM AUTHOR]

Due to the increasing prevalence of life-threatening bacterial, fungal and viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compunds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable compounds for this task are usually derived from natural sources (animal, plant or even microbial). In this review article, the latest and most promising natural compounds used to combat bacteria, filamentous fungi and viruses are presented and evaluated. These include plant extracts, essential oils, small antimicrobial peptides of animal origin, bacteriocins and various groups of plant compounds (triterpenoids; alkaloids; phenols; flavonoids) with antimicrobial and antiviral activity. Data are presented on the inhibitory activity of each natural antimicrobial substance and on the putative mechanism of action against bacterial and fungal strains. The results show that among the bioactive compounds studied, triterpenoids have significant inhibitory activity against coronaviruses, but flavonoids have also been shown to inhibit SARS-COV-2. The last chapter is devoted to nanocarriers used to improve stability, bioavailability, cellular uptake/internalization, pharmacokinetic profile and reduce toxicity of natural compunds. There are a number of nanocarriers such as liposomes, drug delivery microemulsion systems, nanocapsules, solid lipid nanoparticles, polymeric micelles, dendrimers, etc. However, some of the recent studies have focused on the incorporation of natural substances with antimicrobial/antiviral activity into polymeric nanoparticles, niosomes and silver nanoparticles (which have been shown to have intrinsic antimicrobial activity). The natural antimicrobials isolated from animals and microorganisms have been shown to have good inhibitory effect on a range of pathogens, however the plants remain the most prolific source. Even if the majority of the studies for the biological activity evaluation are in silico or in vitro , their internalization in the optimum nanocarriers represents the future of "green therapeutics" as shown by some of the recent work in the field. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) continues to have a profound global health impact. New infections continue at a high rate despite the development of prophylactic therapies, prompting the need for development of novel preventative approaches. Antimicrobial peptides (AMPs), such as LL-37, display broad microbicidal properties and have potential as anti-HIV agents. LL-37 has been studied for its anti-HIV activity and the limited data available suggest it can inhibit HIV infection in primary T cells as well as exert inhibitory effects on key HIV enzymes. Its immunomodulatory properties may both enhance and inhibit HIV replication. In addition, LL-37 has both 1) the ability to kill other sexually-transmitted pathogens and 2) spermicidal activity; thus, it is a good candidate for multipurpose prevention technology. Further investigation of its anti-HIV activity is warranted. [ABSTRACT FROM AUTHOR]

Aim: The present study aims to evaluate the potential antioxidant and antiproliferative properties of probiotic bacterial isolates Weissella cibaria p3B, Bacillus subtilis CS, and Bacillus tequilensis CL, isolated from South Indian fermented tomato pickle (homemade) and gut content of indigenous country chicken. Methods and Results: The bacterial isolates exhibited antimicrobial activity against food‐borne, human pathogenic bacteria, along with better survival under different bile and acidic conditions, hydrophobicity towards several hydrocarbons, and adherence to intestinal epithelial cells (INT‐407 cells). Also, the intact cell (IC) mixture of the three species showed better DPPH, ABTS, and Fe2+ chelating activity as compared to the individual IC or cell extract (CE) activity. Among the three bacterial species, W. cibaria p3B revealed maximum antiproliferative activity against HeLa and Caco‐2 cancer cells, all of which were nontoxic to INT‐407 cells. Apart from being non‐hemolytic, the bacterial isolates did not display any necrotic inhibition in HeLa and Caco‐2 cells. The cell free supernatant (CFS) of the three bacterial isolates were tested for the production of antimicrobial peptides or bacteriocins. It found that the CFS of bacterial isolates was stable at various temperature, pH and sensitive to proteolytic enzymes confirms protenoius in nature of the antimicrobil peptides or bacteriocins. Conclusion: The bacterial isolates showed promising antimicrobial, antioxidant as well as antiproliferative activities with better survival ability at different pH and bile concentrations. The three bacterial isolates were able to produce potential antimicrobial peptides or bacteriocins. Significance and Impact of the study: These results indicate better compatibility of our bacterial isolates against synthetic drugs to avoid adverse side effects and can be processed as dietary supplements against food and human pathogens. They can also provide antioxidative and antiproliferative benefits to humans and animals. [ABSTRACT FROM AUTHOR]

Garlic (Allium sativum L.) is well renowned for its antimicrobial potential and broadly consumed spice globally for its medicinal properties. Moreover, several studies advocate that garlic contains many bioactives that demonstrate strong therapeutic properties in treating cardiovascular diseases, digestive system, diabetes, cancer, obesity, hypertension, inflammation, antioxidant, and viral infection. Presently, therapeutics of natural origin are drawing major interest among consumers due to their antimicrobial efficacy and safety. Garlic extracts, chitosan by- products, several spices and antimicrobial peptides are illustrations for such products. The present review paper inspects briefly the major active ingredients and key biological functions of garlic-based nanoparticles discussing the relevant mechanisms of actions. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are naturally occurring protein molecules with antibacterial, antiviral and/or antifungal activity. Some antimicrobial peptides kill microorganisms through direct binding with negatively charged microbial surfaces. This action disrupts the cytoplasmic membrane and leads to the leakage of the cytoplasm. In addition, they are involved in the innate immune response. Antimicrobial peptides play an important role in oral health, as natural antimicrobial peptides are the first line of host defence in response to microbial infection. The level of natural antimicrobial peptides increases during severe disease conditions and play a role in promoting the healing of oral tissues. However, they are insufficient for eliminating pathogenic micro-organisms. The variability of the oral environment can markedly reduce the effect of natural antimicrobial peptides. Thus, researchers are developing synthetic antimicrobial peptides with promising stability and biocompatibility. Synthetic antimicrobial peptides are a potential alternative to traditional antimicrobial therapy. Pertinent to oral diseases, the deregulation of antimicrobial peptides is involved in the pathogenesis of dental caries, periodontal disease, mucosal disease and oral cancer, where they can kill pathogenic microorganisms, promote tissue healing, serve as biomarkers and inhibit tumor cells. This narrative review provides an overview of the multifaceted roles of antimicrobial peptides in oral diseases. [ABSTRACT FROM AUTHOR]

Bone regeneration remains a major clinical challenge, especially when infection necessitates prolonged antibiotic treatment. This study presents a membrane composed of self-assembled and interpenetrating GL13K, an antimicrobial peptide (AMP) derived from a salivary protein, in a collagen membrane for antimicrobial activity and enhanced bone regeneration. Commercially available collagen membranes were immersed in GL13K solution, and self-assembly was initiated by raising the solution pH to synthesize the multifunctional membrane called COL-GL. COL-GL was composed of interpenetrating large collagen fibers and short GL13K nanofibrils, which increased hydrophobicity, reduced biodegradation from collagenase, and stiffened the matrix compared to control collagen membranes. Incorporation of GL13K led to antimicrobial and anti-fouling activity against early oral surface colonizer Streptococcus gordonii while not affecting fibroblast cytocompatibility or pre-osteoblast osteogenic differentiation. GL13K in solution also reduced macrophage inflammatory cytokine expression and increased pro-healing cytokine expression. Bone formation in a rat calvarial model was accelerated at eight weeks with COL-GL compared to the gold-standard collagen membrane based on microcomputed tomography and histology. Interpenetration of GL13K within collagen sidesteps challenges with antimicrobial coatings on bone regeneration scaffolds while increasing bone regeneration. This strength makes COL-GL a promising approach to reduce post-surgical infections and aid bone regeneration in dental and orthopedic applications. The COL-GL membrane, incorporating the antimicrobial peptide GL13K within a collagen membrane, signifies a noteworthy breakthrough in bone regeneration strategies for dental and orthopedic applications. By integrating self-assembled GL13K nanofibers into the membrane, this study successfully addresses the challenges associated with antimicrobial coatings, exhibiting improved antimicrobial and anti-fouling activity while preserving compatibility with fibroblasts and pre-osteoblasts. The accelerated bone formation observed in a rat calvarial model emphasizes the potential of this innovative approach to minimize post-surgical infections and enhance bone regeneration outcomes. As a promising alternative for future therapeutic interventions, this material tackles the clinical challenges of extended antibiotic treatments and antibiotic resistance in bone regeneration scenarios. [ABSTRACT FROM AUTHOR]

The bacterial nanocellulose (BnC) membranes were produced extracellularly by a novel aerobic acetic acid bacterium Komagataeibacter melomenusus. The BnC was modified in situ by adding carboxymethyl cellulose (CMC) into the culture media, obtaining a BnC-CMC product with denser fibril arrangement, improved rehydration ratio and elasticity in comparison to BnC. The proteolytic enzyme bromelain (Br) and antimicrobial peptide nisin (N) were immobilized to BnC matrix by ex situ covalent binding and/or adsorption. The optimal Br immobilization conditions towards the maximized specific proteolytic activity were investigated by response surface methodology as factor variables. At optimal conditions, i.e. , 8.8 mg/mL CMC and 10 mg/mL Br, hyperactivation of the enzyme was achieved, leading to the specific proteolytic activity of 2.3 U/mg and immobilization efficiency of 39.1 %. The antimicrobial activity was observed against Gram-positive bacteria (S. epidermidis , S. aureus and E. faecalis) for membranes with immobilized N and was superior when in situ modified BnC membranes were used. N immobilized on the BnC or BnC-CMC membranes was cytocompatible and did not cause changes in normal human dermal fibroblast cell morphology. BnC membranes perform as an efficient carrier for Br or N immobilization, holding promise in wound debridement and providing antimicrobial action against Gram-positive bacteria, respectively. [ABSTRACT FROM AUTHOR]

[Display omitted] • Dry heating led to increased glycation and formation of glycated peptides. • Soy and pea peptides differed in sRAGE-binding and antimicrobial capacities. • In digesta, 519 soy and 133 pea antimicrobial peptides were predicted. • In digesta, 9 soy and 6 pea glycated peptides had potential antimicrobial capacity. During infant formula production, proteins are always heated, potentially affecting their digestibility and the bioactivities of resulting peptides. Although plant proteins are a promising dairy alternative for infant formula, they remain understudied, necessitating further investigations. Therefore, this research aimed to fill this gap by assessing the impact of different heating modes on soy protein (SP) and pea protein (PP), focusing on glycation levels, peptide formation during in vitro infant digestion, and immune protection potential (sRAGE-binding and antimicrobial activities) of the resulting peptides. Consequently, dry heating led to increased glycation and glycated peptide production, particularly with higher glycation in PP than SP. Moreover, PP exhibited an overall stronger sRAGE-binding capacity than SP, regardless of heating and digestion conditions. Regarding antimicrobial activity, both SP and PP-derived peptides displayed reduced effectiveness against Enterobacter cloacae after dry heating. Additionally, Staphylococcus epidermidis was differently inhibited, where PP-derived peptides showed inherent inhibition. The primary determinant of sRAGE-binding and antimicrobial potential in digestion-derived peptides was the protein source. Subsequent bioinformatics analysis predicted 519 and 133 potential antimicrobial peptides in SP and PP, respectively. This study emphasises the importance of protein source for infant formula to ensure infant health. [ABSTRACT FROM AUTHOR]

The global aquaculture industry has significant losses each year due to disease outbreaks. Antibiotics are one of the common methods to treat fish infections, but prolonged use can lead to the emergence of resistant strains. Aeromonas spp. Infections are a common and problematic disease in fish, and members of this genera can produce antibiotic resistant strains. Antimicrobial peptides (AMPs) have emerged as an alternative method to treat and prevent infections and pituitary adenylate cyclase activating polypeptide (PACAP) is a prominent member of this family. The objective of this research was to study PACAP's direct antimicrobial activity and its toxicity in fish cells. Four synthetic variants of the natural PACAP from Clarias gariepinus were tested in addition to the natural variant. The experimental results show a different antimicrobial activity against A. salmonicida and A. hydrophila of each PACAP variant, and for the first time show dependence on the culture broth used. Furthermore, the results suggest that the underlying mechanism of PACAP antimicrobial activity includes a bacterial membrane permeabilizing effect, classifying PACAP as a membrane disruptive AMP. This study also demonstrated that the five PACAP variants evaluated showed low toxicity in vitro , at concentrations relevant for in vivo applications. Therefore, PACAP could be a promising alternative to antibiotics in the aquaculture sector. [Display omitted] • PACAP variants evaluated showed no toxicity at concentrations lower than 25 μM. • Chemical modifications of PACAP modulate the growth inhibition effect on Aeromonas. • The culture broth used in the antimicrobial activity assay affects PACAP activity. • PACAP can be classified as a membrane disruptive antimicrobial peptide. [ABSTRACT FROM AUTHOR]