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In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS. We sought to identify the molecular etiology of the downregulated expression of HTN1. We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of T H 17/T H 22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls. We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22–producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for T H 17/T H 22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating T H 17 cell abundance was normal. Similar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6–dependent STAT3 phosphorylation that is critical for T H 17/T H 22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS. [ABSTRACT FROM AUTHOR]

Antimicrobial peptide (AMP), also called host defense peptide, is a part of the innate immune system in eukaryotic organisms. AMPs are also produced by prokaryotes in response to stressful conditions and environmental changes. They have a broad spectrum of activity against both Gram positive and Gram negative bacteria. They are also effective against viruses, fungi, parasites, and cancer cells. AMPs are cationic or amphipathic in nature, but in recent years cationic AMPs have attracted a lot of attention because cationic AMPs can easily interact with negatively charged bacterial and cancer cell membranes through electrostatic interaction. AMPs can also eradicate bacterial biofilms and have broad-spectrum activity against multidrug resistant (MDR) bacteria. Although the main target site for AMPs is the cell membrane, they can also disrupt bacterial cell walls, interfere with protein folding and inhibit enzymatic activity. In recent centuries antibiotics are gradually losing their potential because of the continuous rise of antibiotic resistant bacteria. Therefore, there is an urgent need to develop novel therapeutic approaches to treat MDR bacteria, and AMP is such an alternative treatment option over conventional antibiotics. Several communicable diseases like tuberculosis and non-communicable diseases such as cancer can be treated by using AMPs. One of the major advantages of using AMP is that it works with high specificity and does not cause any harm to normal tissue. AMPs can be modified to improve their efficacy. In this narrative review, we are focusing on the potential application of AMPs in medical science. [ABSTRACT FROM AUTHOR]

Biofilm infection and impaired healing of chronic wounds are posing tremendous challenges in clinical practice. In this study, we presented a versatile antimicrobial hydrogel capable of delivering nitric oxide (NO) in a controllable manner to dissipate biofilms, eliminate microorganisms, and promote the healing of chronic wounds. This hydrogel was constructed by Schiff-base crosslinking of oxidized dextran and antimicrobial peptide ε-poly-lysine, further encapsulating photothermal nanoparticles bearing NO donor. This hydrogel could continuously and slowly release NO, effectively dissipating biofilms, and promoting the proliferation of mouse fibroblasts and the migration of endothelial cells. Upon exposure to NIR laser irradiation, the hydrogel generated hyperthermia and rapidly released NO, resulting in the efficient elimination of a broad spectrum of drug-resistant Gram-positive/negative bacterial and fungal biofilms through the synergistic effects of NO, photothermal therapy, and the antibacterial peptide. Notably, the hydrogel demonstrated exceptional in vivo therapeutic outcomes in accelerating the healing process of mice diabetic wounds infected with methicillin-resistant Staphylococcus aureus by successfully eliminating biofilm infection, regulating inflammation, and facilitating angiogenesis and collagen deposition. Overall, this proposed hydrogel shows great promise in accommodating the various demands of the complex repair process of chronic wounds infected with biofilms. The presence of biofilm infections and underlying dysfunctions in the healing process made chronic wound become stuck in the inflammation stage and difficult to heal. This work developed a NIR laser-modulated three-stage NO-releasing versatile antimicrobial hydrogel (DEPN) exhibiting good therapeutic efficacy for chronic wound. This DEPN hydrogel could inherently and slowly released NO to disperse biofilm. Upon NIR laser irradiation, the DEPN hydrogel generated hyperthermia and induced a rapid burst release of NO effectively eliminating a broad spectrum of drug-resistant bacterial and fungal biofilms. Subsequently, the DEPN hydrogel continually release NO slowly to promote the tissue remolding. This DEPN hydrogel displays great potential in treatment of chronic wounds infected with biofilm. [Display omitted] [ABSTRACT FROM AUTHOR]

Dental plaque is the main cause leading to the dental caries and periodontal diseases. The main purpose of this study was to test the efficacy of oral spray containing the antimicrobial peptide P-113 on the reduction of oral bacteria number and dental plaque formation in a randomized clinical assessment. This study was divided into two parts. In Part A, we investigated the user experiences with the P-113 containing oral spray. In part B, 14 subjects in the experimental group used the P-113-containing oral spray, while 14 subjects in the control group used a placebo without the P-113 in a 4-week clinical trial. Participants were asked to use the P-113-containing oral spray or placebo 3 times per day and 5 times per use. Moreover, 3 check-ups and 2 washouts were carried out to evaluate the DMFT score, dental plaque weight, dental plaque index, and gingival index. In part A, up to 91.8% of the subjects in the experimental group were satisfied with the use of the P-113-containing oral spray. In part B, based on our PacBio SMRT sequencing platform and DADA2 analysis, the numbers of Streptococcus and Porphyromonas in the experimental group were lower than those in the control group. In addition, decreased dental plaque weight, dental plaque index, and gingival index were all observed in the experimental group. The P-113-containing oral spray has the potential to reduce the dental caries and periodontal disease-related bacteria and to control the dental plaque formation. [ABSTRACT FROM AUTHOR]

Owing to their limited accuracy and narrow applicability, current antimicrobial peptide (AMP) prediction models face obstacles in industrial application. To address these limitations, we developed and improved an AMP prediction model using Comparing and Optimizing Multiple DEep Learning (COMDEL) algorithms, coupled with high-throughput AMP screening method, finally reaching an accuracy of 94.8% in test and 88% in experiment verification, surpassing other state-of-the-art models. In conjunction with COMDEL, we employed the phage-assisted evolution method to screen Sortase in vivo and developed a cell-free AMP synthesis system in vitro , ultimately increasing AMPs yields to a range of 0.5–2.1 g/L within hours. Moreover, by multi-omics analysis using COMDEL, we identified Lactobacillus plantarum as the most promising candidate for AMP generation among 35 edible probiotics. Following this, we developed a microdroplet sorting approach and successfully screened three L. plantarum mutants, each showing a twofold increase in antimicrobial ability, underscoring their substantial industrial application values. This study establishes an AI-based AMPs prediction model named COMDEL for effectively mining edible AMPs and probiotics, which are subsequently synthesized and directly evolved for industrial application, respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

The emergence of antibiotic-resistant bacteria is a serious threat to public health. Antimicrobial peptides (AMP) are a powerful alternative to antibiotics due to their low propensity to induce bacterial resistance. However, cytotoxicity and short half-lives have limited their clinical translation. To overcome these problems, AMP conjugation has gained relevance in the biomaterials field. Nevertheless, few studies describe the influence of conjugation on enzymatic protection, mechanism of action and antimicrobial efficacy. This review addresses this gap by providing a detailed comparison between conjugated and soluble AMP. Additionally, commonly employed chemical reactions and factors to consider when promoting AMP conjugation are reviewed. The overall results suggested that AMP conjugated onto biomaterials are specifically protected from degradation by trypsin and/or pepsin. However, sometimes, their antimicrobial efficacy was reduced. Due to limited conformational freedom in conjugated AMP, compared to their soluble forms, they appear to act initially by creating small protuberances on bacterial membranes that may lead to the alteration of membrane potential and/or formation of holes, triggering cell death. Overall, AMP conjugation onto biomaterials is a promising strategy to fight infection, particularly associated to the use of medical devices. Nonetheless, some details need to be addressed before conjugated AMP reach clinical practice. Covalent conjugation of antimicrobial peptides (AMP) has been one of the most widely used strategies by bioengineers, in an attempt to not only protect AMP from proteolytic degradation, but also to prolong their residence time at the target tissue. However, an explanation for the mode of action of conjugated AMP is still lacking. This review extensively gathers works on AMP conjugation and puts forward a mechanism of action for AMP when conjugated onto biomaterials. The implications of AMP conjugation on antimicrobial activity, cytotoxicity and resistance to proteases are all discussed. A thorough review of commonly employed chemical reactions for this conjugation is also provided. Finally, details that need to be addressed for conjugated AMP to reach clinical practice are discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC), one of the diarrheagenic E. coli , is the most common cause of diarrhea in developing country and in travelers to those areas. In this study, Caenorhabditis elegans was used as an alternative model host to evaluate ETEC infections. The ETEC strain ETEC1, which was isolated from a patient with diarrhea, possessed enterotoxins STh, LT1, and EAST1 and colonization factors CS2 and CS3. Live ETEC1 shortened the life span and body size of C. elegans in association with increased expression of enterotoxin genes and intestinal colonization. In contrast, heat-killed ETEC1 did not affect the life span of C. elegans. Caenorhabditis elegans infected with ETEC1 showed upregulated expression of genes related to insulin-like peptides and host defense responses. These results suggest that ETEC1 exhibits pathogenicity through intestinal colonization and enterotoxin production in C. elegans. This system is useful as an ETEC infection model. [ABSTRACT FROM AUTHOR]

The components of milk from beef cows remain to be elucidated. This study examined the differences in the antimicrobial components of milk between dairy and beef cows. Quarter milk was collected from both Japanese Black (beef type) and Holstein (dairy type) cows to compare the concentrations of antimicrobial components. The concentration of lingual antimicrobial peptide (LAP) was higher, whereas that of the other antimicrobial components (lactoferrin, S100A7, and S100A8) was lower in beef cows than in dairy cows. Overall, these results indicate that the differences in antimicrobial components between beef and dairy cows may be associated with the difference in the prevalence of mastitis between them. [ABSTRACT FROM AUTHOR]

Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G+) and Gram-negative (G–) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G– bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria. Schematic illustration of TPI-CysHHC10 comprising AMPs and AIE photosensitizer as a photoactivatable, broad-spectrum, antibacterial agent for combating biofilms. [Display omitted] [ABSTRACT FROM AUTHOR]

Bee venom (BV) extraction has become a standardized practice, characterized by being safe, simple, and causing no harm to bees. Though it demonstrated significant antimicrobial activity, its potential activity against honey bee pathogens have yet to be investigated. Therefore, we investigated for the first time in a controlled laboratory setting the effectiveness of BV administration in sugar syrup against Vairimorpha (Nosema) ceranae, a globally widespread fungal disease of honey bees. To do this, we first determined the BV lethal concentration (LC50), after which newly emerged bees were inoculated with V. ceranae spores (105) or/and chronically fed sugar syrup containing BV at LC10 (0.24 mg/mL) or LC20 (0.34 mg/mL) ad libitum for 12 days. The effects on bee longevity (time to death) were studied. The intensity of V. ceranae and total hemocyte count (THC) were also studied 6 and 12 days after infection. The expression of four antimicrobial peptides (AMPs) encoding genes (defensin1, apismin, hymenopteacin, and PGRPS2) was also measured after 6 days in midgut tissues. We discovered that BV increased bee survival and significantly reduced Vairimorpha intensity. This effect was associated with an increase in THC as well as the expression of the AMP-encoding genes studied. BV’s effects appeared to be concentration- and time-dependent, with a more profound decrease in Vairimorpha intensity at day 12, especially in bees fed BV at LC20. These findings highlight BV’s potent immunomodulatory role against fungal pathogens in honey bees, and its potential role against other bacterial and viral pathogens should be investigated. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is an infection-driven inflammatory disease in which the composition of biofilms plays a significant role. Dental plaque accumulation at the gingival margin initiates an inflammatory response that, in turn, causes microbial alterations and may lead to drastic consequences in the periodontium of susceptible individuals. Antimicrobial peptides protect the host against various pathogens such as bacteria, viruses, fungi and yeast. Antimicrobial peptides also display immunomodulatory properties ranging from the modulation of inflammatory responses to the promotion of wound healing. Aim of Study: The purpose of this review is to outline the function of the antimicrobial peptides (cathelicidin, human neutrophil peptides 1-3 and human beta defensin-1) in periodontitis patients. Methodology: Using suitable keywords, relevant papers would be searched in the scientific databases Scopus, Google Scholar, PubMed, and Web of Science. Results: Covered studies were posted between 2000 and 2022 and detect great variance in patients selection, clinical assessments, and antimicrobial peptides measures. A significant association between antimicrobial peptides and periodontitis developments was reported in some studies. Conclusion: antimicrobial peptides play a crucial role [ABSTRACT FROM AUTHOR]

Background Antimicrobial peptides (AMPs), innate immune response molecules in organisms, are also known for their dual functionality, exemplified by hepcidin--an immunomodulator and iron regulator. Identifying and studying various AMPs from fish species can provide valuable insights into the immune profiles of aquaculturally significant fish, which can be made use of in its culture. Results Hepcidin, a dual-function antimicrobial peptide, was isolated from the gill tissue of Genetically Improved Farmed Tilapia (GIFT-Hep). GIFT-Hep consists of a 90 amino acid pre-propeptide with a 24-mer signal, a 40-mer propeptide, and a 26-mer mature peptide region. The mature peptide had a molecular weight of 3015.61 Da, a theoretical pI of 8.78, a net charge of +4.25, and a protein-binding potential of 2.06 kcal/mol. Four disulfide bonds were formed by eight cysteine residues in the mature region. The presence of positively charged arginine residues renders the peptide 50% hydrophobic. Molecular analysis of GIFT-Hep revealed the presence of a furin propeptide convertase motif, RX(K/R)R, which facilitates trimming of the peptide to yield the mature GIFT-Hep. The hypothetical iron regulatory sequence, QSHLSL, was also identified in the mature peptide. In silico predictions about the characteristics of GIFT-Hep, such as charge, hydrophobicity, high surface accessibility, transmembrane helical regions, hydrophobic faces, hot spots, and cell-penetrating properties, suggest that the peptide functions as an iron regulatory antimicrobial agent. Conclusions This study reports a hepcidin antimicrobial peptide with both HAMP1 and HAMP2 properties isolated from genetically improved farmed tilapia, and further evaluation of the properties will prove the feasibility of GIFT-Hep being used as a therapeutant in aquaculture. [ABSTRACT FROM AUTHOR]

Recent data suggest that the orexigenic peptide ghrelin and liverexpressed antimicrobial peptide 2 (LEAP2) have opposing effects on food intake regulation. Although circulating ghrelin is decreased in obesity, peripheral ghrelin administration does not induce food intake in obese mice. Limited information is available on ghrelin resistance in relation to LEAP2. In this study, the interplay between ghrelin and LEAP2 in obesity induced by a high-fat (HF) diet in mice was studied. First, the progression of obesity and intolerance to glucose together with plasma levels of active and total ghrelin, leptin, as well as liver LEAP2 mRNA expression at different time points of HF diet feeding was examined. In addition, the impact of switch from a HF diet to a standard diet on plasma ghrelin and LEAP2 production was studied. Second, sensitivity to the stable ghrelin analogue [Dpr3 ]Ghrelin or our novel LEAP2 analogue palm-LEAP2(1-14) during the progression of HF diet-induced obesity and after the switch for standard diet was investigated. Food intake was monitored after acute subcutaneous administration. HF diet feeding decreased both active and total plasma ghrelin and increased liver LEAP2 mRNA expression along with intolerance to glucose and the switch to a standard diet normalized liver LEAP2 mRNA expression and plasma level of active ghrelin, but not of total ghrelin. Additionally, our study demonstrates that a HF diet causes resistance to [Dpr³ ]Ghrelin, reversible by switch to St diet, followed by resistance to palm-LEAP2(1-14). Further studies are needed to determine the long-term effects of LEAP2 analogues on obesity-related ghrelin resistance. [ABSTRACT FROM AUTHOR]

Immunostimulants and vaccines are the main means for controlling infectious diseases and searching highly effective and low toxic immunestimulants has always been the focus of researchers. The MetchnikowinII (MetII) had been expressed by us and exhibited both antibacterial and antifungal activities, in this study, we evaluated its potential for an adjuvant effect. In chickens, antigen-specific immunoglobulin Gs (IgGs) were increased after MetII adjuvanted vaccination using the Ptfa protein. Compared to group Ptfa + iFA, which was only adjuvanted with incomplete Freund's adjuvant (iFA), the antibody titers of the group Ptfa + iFA + Met20 µg·mL-1 (PFM20) and Ptfa + iFA + Propolis (PFP) significantly increased (P<0.05). Likewise, Interleukin-2 (IL-2) and Interferon-y (IFN-y) cytokines in group Ptfa + iFA + Met20 µg·mL-1 (PFM20) and Ptfa + iFA + Propolis (PFP) were significantly higher than those of the other three experimental groups (P<0.05). The stimulation index (SI) value in chickens of group PFM20 was significantly higher than that of the other four experimental groups (P<0.05). Chickens that received MetII adjuvanted vaccinations benefitted from higher protection rate (88%) when challenged with Pasteurella multocida (P. multocida), which was significantly higher than those of group PF and PFP (P<0.05). These results suggested that the antimicrobial peptide MetII may play an adjuvant role in the immune response in chickens but need a proper usage, because the higher usage of 40 µg·mL-1 and 60 µg·mL-1 resulted poor effect. Whether MetII could be a potential adjuvant or a biomolecule as part of a complex adjuvant for vaccines needs more experimental evidence, the study still provides an examples for understanding vaccine adjuvants. [ABSTRACT FROM AUTHOR]

Recently, much emphasis has been placed on solving the intrinsic defects of antimicrobial peptides (AMPs), especially their susceptibility to protease digestion for the systemic application of antibacterial biomaterials. Although many strategies have increased the protease stability of AMPs, antimicrobial activity was severely compromised, thereby substantially weakening their therapeutic effect. To address this issue, we introduced hydrophobic group modifications at the N-terminus of proteolysis-resistant AMPs D1 (AArIIlrWrFR) through end-tagging with stretches of natural amino acids (W and I), unnatural amino acid (Nal) and fatty acids. Of these peptides, N1 tagged with a Nal at N-terminus showed the highest selectivity index (GM SI =19.59), with a 6.73-fold improvement over D1. In addition to potent broad-spectrum antimicrobial activity, N1 also exhibited high antimicrobial stability toward salts, serum and proteases in vitro and ideal biocompatibility and therapeutic efficacy in vivo. Furthermore, N1 killed bacteria through multiple mechanisms, involving disruption of bacterial membranes and inhibition of bacterial energy metabolism. Indeed, appropriate terminal hydrophobicity modification opens up new avenues for developing and applying high-stability peptide-based antibacterial biomaterials. To improve the potency and stability of proteolysis-resistant antimicrobial peptides (AMPs) without increasing toxicity, we constructed a convenient and tunable platform based on different compositions and lengths of hydrophobic end modifications. By tagging an Nal at the N-terminal, the obtained target compound N1 exhibited strong antimicrobial activity and desirable stability under multifarious environments in vitro (proteases, salts and serum), and also showed favorable biocompatibility and therapeutic efficacy in viv o. Notably, N1 exerted its bactericidal effect by damaging bacterial cell membranes and inhibiting bacterial energy metabolism in a dual mode. The findings provide a potential method for designing or optimizing proteolysis-resistant AMPs thus promoting the development and application of peptide-based antibacterial biomaterial. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • M. anisopliae phenylethyl alcohol exerts an avoidance effect to locusts. • M. anisopliae infection elevates the expression of LmOBP11 in locusts. • Treatment with phenylethyl alcohol upregulates LmOBP11 in locusts. • Locust LmOBP11 is involved in the detection of fungal phenylethyl alcohol. • LmOBP11 negatively regulates the locust immune system to benefit fungal infection. Odorant-binding proteins (OBPs) are a class of small molecular weight soluble proteins that exist as expanded gene families in all insects, acting as ligand carriers mediating olfaction and other physiological processes. During fungal infection, a subset of insect OBPs were shown to be differentially expressed. We tested whether the altered expression of insect OBP s during pathogenic infection plays a role in behavioral or immune interactions between insect hosts and their pathogens. A wide range of techniques including RNAi-directed knockdown, heterologous protein expression, electrophysiological/behavioral analyses, transcriptomics, gut microbiome analyses, coupled with tandem mass spectrometry ion monitoring, were used to characterize the function of a locust OBP in host behavioral and immune responses. The entomopathogenic fungus Metarhizium anisopliae produces the volatile compound phenylethyl alcohol (PEA) that causes behavioral avoidance in locusts. This is mediated by the locust odorant binding protein 11 (LmOBP11). Expression of LmOBP11 is induced by M. anisopliae infection and PEA treatment. LmOBP11 participates in insect detection of the fungal-produced PEA and avoidance of PEA-contaminated food, but the upregulation of LmOBP11 upon M. anisopliae infection negatively affects the insect immune responses to ultimately benefit successful mycosis by the pathogen. RNAi knockdown of LmOBP11 increases the production of antimicrobial peptides and enhances locust resistance to M. anisopliae infection, while reducing host antennal electrophysiological responses to PEA and locust avoidance of PEA treated food. Also, transcriptomic and gut microbiome analyses reveal microbiome dysbiosis and changes in host genes involved in behavior and immunity. These results are consistent with the elevated expression of LmOBP11 leading to enhanced volatile detection and suppression of immune responses. These findings suggest a crosstalk between olfaction and immunity, indicating manipulation of host OBPs as a novel target exploited by fungal pathogens to alter immune activation and thus promote the successful infection of the host. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance is a significant public health concern around the globe. Antimicrobial peptides exhibit broad-spectrum and efficient antibacterial activity with an added advantage of low drug resistance. The higher water content and 3D network structure of the hydrogels are beneficial for maintaining antimicrobial peptide activity and help to prevent degradation. The antimicrobial peptide released from hydrogels also hasten the local wound healing by promoting epithelial tissue regeneration and granulation tissue formation. Objective: This study aimed at developing sodium alginate based hydrogel loaded with a novel antimicrobial peptide Chol-37(F34-R) and to investigate the characteristics in vitro and in vivo as an alternative antibacterial wound dressing to treat infectious wounds. Methods: Hydrogels were developed and optimized by varying the concentrations of crosslinkers and subjected to various characterization tests like cross-sectional morphology, swelling index, percent water contents, water retention ratio, drug release and antibacterial activity in vitro, and Pseudomonas aeruginosa infected wound mice model in vivo. Results: The results indicated that the hydrogel C proved superior in terms of cross-sectional morphology having uniformly sized interconnected pores, a good swelling index, with the capacity to retain a higher quantity of water. Furthermore, the optimized hydrogel has been found to exert a significant antimicrobial activity against bacteria and was also found to prevent bacterial infiltration into the wound site due to forming an impermeable barrier between the wound bed and external environment. The optimized hydrogel was found to significantly hasten skin regeneration in animal models when compared to other treatments in addition to strong inhibitory effect on the release of pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). Conclusions: Our results suggest that sodium alginate -based hydrogels loaded with Chol37(F34-R) hold the potential to be used as an alternative to conventional antibiotics in treating infectious skin wounds. [ABSTRACT FROM AUTHOR]

Dysfunction of the intestinal mucosal immune system and dysbiosis of the intestinal microflora can induce inflammatory bowel disease. However, drug-mediated clinical treatment remains a challenge due to its poor therapeutic efficacy and severe side effects. Herein, a ROS scavenging and inflammation-directed nanomedicine is designed and fabricated by coupling polydopamine nanoparticles with mCRAMP, an antimicrobial peptide, while wrapping macrophage membrane in the outer layer. The designed nanomedicine reduced the secretion of pro-inflammatory cytokines and elevate the expression of anti-inflammatory cytokine in vivo and in vitro inflammation models, demonstrating its significant ability of improving inflammatory responses. Importantly, the macrophage membrane encapsulated nanoparticles exhibit the obviously enhanced targeting performance in local inflamed tissues. Furthermore, the 16S rRNA sequencing of fecal microorganisms showed that probiotics increased and pathogenic bacteria were inhibited after oral delivery the nanomedicine, indicating that the designed nano platform played a significant role in optimizing intestinal microbiome. Taken together, the designed nanomedicine are not only easy to prepare and exhibit high biocompatibility, but also show the inflammatory targeting property, anti-inflammatory function and positive regulation of intestinal flora, thus providing a new idea for the intervention and treatment of colitis. Inflammatory bowel disease (IBD), a chronic and intractable disease, may lead to colon cancer in severe cases without effective treatment. However, clinical drugs are largely ineffective owing to insufficient therapeutic efficacies and side effects. Herein, we constructed a biomimetic polydopamine nanoparticle for oral administration to treat the IBD by modulating mucosal immune homeostasis and optimizing intestinal microorganisms. In vitro and in vivo experiments showed that the designed nanomedicine not only exhibits the anti-inflammatory function and inflammatory targeting property but also positively regulate the gut microflora. Taken together, the designed nanomedicine combined immunoregulation and intestinal microecology modulation to significantly enhance the therapeutic effect on colitis in mice, thus providing a new approach for the clinical treatment of colitis. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Allergic fungal rhinosinusitis (AFRS) is an endotype of chronic rhinosinusitis (CRS) with nasal polyps characterized by eosinophilic mucin laden with fungal hyphae entrapped in expanded sinus cavities with an exaggerated hypersensitivity to fungal elements. The last decade has elucidated fungi-driven inflammatory pathways contributing to the pathophysiology of chronic inflammatory respiratory diseases. In addition, novel therapeutic biologic options have become available for CRS over the last several years. Objective: To review the current literature examining AFRS, focusing on recent developments in our understanding of its pathophysiology and implications for treatment options. Methods: Review article. Results: Fungi-driven respiratory inflammation has been linked to fungal proteinases and toxin activity. In addition, AFRS patients demonstrate a local sinonasal immunodeficiency in antimicrobial peptides and hence limited antifungal activity, along with an exaggerated type 2 inflammatory response, highlighting a possible imbalanced type 1, type 2, and type 3 profile. The elucidation of these dysregulated molecular pathways has highlighted novel potential therapeutic targets. As such, the clinical management of AFRS, which once included surgery and extended courses of oral corticosteroids, is transitioning away from long courses of oral corticosteroids to incorporate novel delivery mechanisms of topical therapeutic targets and biologics for recalcitrant disease. Conclusion: AFRS is an endotype of CRS with nasal polyps (CRSwNP) for which the molecular pathways leading to its inflammatory dysfunction are beginning to be illuminated. In addition to affecting treatment options, these understandings may shape necessary changes to diagnostic criteria and the extrapolated effects of environmental changes on AFRS. More critically, a better appreciation of fungi-driven inflammatory pathways may have implications for the understanding of broader CRS inflammation. [ABSTRACT FROM AUTHOR]

Background: Invertebrates like crabs employ their own immune systems to fight against a number of invasive infections. Anti-lipopolysaccharide factors (ALFs) are an important class of antimicrobial peptides (AMPs) exhibiting binding and neutralizing activities against lipopolysaccharides. Results: This study identified and characterized a novel homolog of ALF (Pp-ALF) from the blue swimmer crab Portunus pelagicus. Pp-ALF has a 369bp open-reading frame encoding a protein with 123 amino acids. The deduced protein featured an LPS-binding domain and a signal peptide. The predicted tertiary structure of Pp-ALF contains three α helices packed against four β sheets. The deduced amino acid sequence of Pp-ALF had a net positive charge of +10.75 and an isoelectric point of 9.8. Phylogenetic analysis revealed that Pp-ALF has a strong ancestral relationship with crab ALFs. Conclusion: Antibacterial, antiviral, antifungal, anticancer, and antibiofilm activities of Pp-ALF could be revealed by in silico prediction tools. Recombinant expression of Pp-ALF was unsuccessful in the Escherichia coli Rosetta-gami expression system due to the cytotoxic effect of the peptide to the host. The toxic effect of Pp-ALF to the host was displayed by membrane permeabilization and death of the host cells by fluorescent staining with Syto9-Propidium Iodide and CTC-DAPI- FITC. [ABSTRACT FROM AUTHOR]

Infections induced by intracellular pathogens are difficult to eradicate due to poor penetration of antimicrobials into cell membranes. It is of great importance to develop a new generation of antibacterial agents with dual functions of efficient cell penetration and bacterial inhibition. In this study, the association between hydrophobicity and cell-penetrating peptide delivery efficiency was investigated by fragment interception and hydrophobicity modification of natural porcine antimicrobial peptide PR-39 and the combination of cationic cell-penetrating peptide (R6) with antimicrobial peptide fragments modified with hydrophobic residues. The chimeric peptides P3I7 and P3L7, obtained through biofunctional screening, exhibited potent broad-spectrum antibacterial activity and low cytotoxicity. Moreover, P3I7 and P3L7 can effectively penetrate cells to eliminate intracellular pathogens mainly through endocytosis. The membrane destruction mechanism makes the peptides fast sterilizers and less prone to developing drug resistance. Finally, their good biocompatibility and antibacterial infection effects were verified in mice and piglets. To conclude, the chimeric peptides P3I7 and P3L7 show great potential as affordable and effective antimicrobial agents and may serve as ideal candidates for the treatment of intracellular bacterial infections. The low permeability of antibacterial drugs makes infections induced by intracellular bacteria extremely difficult to treat. To address this issue, we designed chimeric peptides with dual cell-penetrating and antibacterial functions. The active peptides P3I7 and P3L7, acquired through functional screening have strong broad-spectrum antibacterial activity and powerful bactericidal effects against intracellular Staphylococcus aureus. The membrane permeation mechanism of P3I7 and P3L7 against bacteria endows fast bactericidal activity with low drug resistance. The biosafety and antibacterial activity of P3I7 and P3L7 were also validated by in vivo trials. This study provides an ideal drug candidate against intracellular bacterial infections. [Display omitted] [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) show broad-spectrum microbicidal activity against bacteria, fungi, and viruses, and have been considered as one of the most promising candidates to overcome bacterial antimicrobial resistance. Structural modification of AMPs is an effective strategy to develop high-efficiency and low-toxicity antibacterial agents. A series of peptides GHaR6R, GHaR7R, GHaR8R, and GHaR9W with arginine replacement of histidine (His) derived from temporin-GHa of Hylarana guentheri were designed and synthesized. These derived peptides exhibit antibacterial activity against Staphylococcus aureus, and GHaR8R exerts bactericidal effect within 15 min at 4 × MIC (25 μm). The derived peptides caused rapid depolarization of bacteria, and the cell membrane damage was monitored using quartz crystal microbalance with dissipation assay, which suggests that they target cell membranes to exert antibacterial effects. The derived peptides can effectively eradicate mature biofilms of S. aureus. Taken together, the derived peptides are promising antibacterial agent candidates against S. aureus. [ABSTRACT FROM AUTHOR]

The management of wound infection remains the major challenges in real-time diagnosis, effective bacterial elimination and rapid wound healing. Herein, we developed injectable theranostic hydrogels to achieve long-term visual imaging of infected wounds and possible infection recurrence and to launch an on-demand bactericidal effect without using any antibiotics. Antimicrobial peptide ε-polylysine (ePL)-derived hydrogels were prepared through the copolymerization of methacrylated ePL (mPL) and the conjugates with tetrakis(4-carboxyphenyl) porphyrin (mPL-TCPP) and phenol red (mPL-Pr). Light illumination of mPL-TCPP produces reactive oxidative species (ROS) to initiate free radical crosslinking into PL@Pr-TCPP hydrogels without using any additional photoinitiators and concurrently exhibits antibacterial photodynamic therapy (PDT). PL@Pr-TCPP hydrogels experience quick color changes from yellow to orange and finally to red when pH values change from 5.0 to 9.0. The actual pH and related bacterial levels in the wounds could be read from G/B signal ratios of hydrogel colors captured by a smart phone. The conjugation of phenol red and TCPP into hydrogels affords a robust bacterial infection diagnosis and persistent bactericidal effect after cycled light illumination. The bacterial capture by ePL hydrogels strengthens PDT effect through alleviating the short lifetime and action distance of ROS. On a Staphylococcus aureus -infected abscess model, light illumination of the pregel solutions achieves in situ formation of hydrogel dressings. The synergistic bactericidal performance significantly relieves inflammatory status, accelerates collagen deposition, and promotes neovascularization, leading to full recovery of the infected wounds with regeneration of skin accessories. PL@Pr-TCPP hydrogels on the wound bed show color changes upon the recurrence of bacterial infection, which could also be totally eliminated after light illumination. Therefore, this study demonstrates a feasible strategy to develop theranostic hydrogel dressings for life-cycle diagnosis and on-demand treatment of wound infections. Over 30% of skin and soft tissue infections become chronic even after appropriate antibacterial treatment, and recurrent infections are commonly reported after initial infection. Challenges remain in the development of theranostic wound dressings having the capability of point-of-care diagnosis, life-cycle monitoring and on-demand elimination of bacterial infection. Herein, light-triggered gelation is used to develop theranostic hydrogels for reversible naked-eye diagnosis and on-demand photodynamic therapy of wound infections. Light illumination plays a "one-stone-two-birds" role, i.e., photodynamically produced reactive oxidative species enable bactericidal effect without using any antibiotics, and the generated free radicals initiate crosslinking of hydrogels without using any additional photoinitiators. Bacterial infection-activated color changes of hydrogels could be captured with a smart phone for on-site and persistent monitoring of bacterial infection and wound healing process. [Display omitted] [ABSTRACT FROM AUTHOR]

Preventing initial colonization of bacteria on biomaterial surfaces is crucial to address the medical device-associated infection issues. Antimicrobial peptide (AMP) or cationic polymer modified surfaces have shown promising potentials to inhibit the initial colonization of bacteria by contact killing. However, their development has been impeded because of bacterial adhesion and high cytotoxicity. Herein, we report a series of brush polypeptide coatings with anionic backbones and cationic AMP mimetic side-chains that displayed superior bactericidal activity, antibacterial adhesion property, and biocompatibility. The cationic side-chain density played an important role in the bioactivities of the brush polypeptide modified surfaces. Brush polypeptide coating with low side-chain density exhibited improved bactericidal activity and antibacterial adhesion property, ascribing to the cooperative effects of adjacent side-chains and backbones/side-chains, respectively. It also showed negligible hemolysis/cytotoxicity in vitro and potent anti-infection property (≥99.9% bactericidal efficacy) in vivo. Brush polymers with anionic backbones and cationic side-chains can be used as a promising design motif to potentiate both antibacterial property and biocompatibility of coatings for combating device-associated infections. Device-associated infections (DAIs) have led to increased medical cost, pain, and even mortality of patients. Antimicrobial peptide and cationic polymer coatings provide an important strategy to combat DAIs by preventing initial colonization of bacteria on biomaterial surfaces. Nevertheless, they have suffered bacterial adhesion and cytotoxicity issues. Herein, we developed a brush polypeptide coating with anionic backbones and cationic side-chains. The brush polypeptide coating showed superior bactericidal and antibacterial adhesion properties outperforming conventional antibacterial coatings based on antimicrobial peptide (i.e., melittin), lysozyme (i.e., lysostaphin), cationic polymer, anionic polymer, and the blends of cationic/anionic polymers. It also showed good biocompatibility and potent anti-infection property, making it a promising candidate to combat the DAIs. [Display omitted] [ABSTRACT FROM AUTHOR]

The increasingly severe bacterial resistance worldwide pushes people to discover and design potential antibacterial drugs unavoidably. In this work, a series of short, mirror-symmetric peptides were designed and successfully synthesized, centered on "RRR" and labeled with hydrophobic amino acids at both ends. Based on the structure-activity relationship analysis, LWWR (LWWRRRWWL-NH 2) was screened as a desirable mirror-symmetric peptide for further study. As expected, LWWR displayed broad-spectrum antibacterial activity against the standard bacteria and antibiotic-resistant strains. Undoubtedly, the high stability of LWWR in a complex physiological environment was an essential guarantee to maximizing its antibacterial activity. Indeed, LWWR also exhibited a rapid bactericidal speed and a low tendency to develop bacterial resistance, based on the multiple actions of non-receptor-mediated membrane actions and intra-cellular mechanisms. Surprisingly, although LWWR showed similar in vivo antibacterial activity compared with Polymyxin B and Melittin, the in vivo safety of LWWR was far higher than that of them, so LWWR had better therapeutic potential. In summary, the desirable mirror-symmetric peptide LWWR was promised as a potential antibacterial agent to confront the antibiotics resistance crisis. Witnessing the growing problem of antibiotic resistance, a series of short, mirror-symmetric peptides based on the symmetric center "RRR" and hydrophobic terminals were designed and synthesized in this study. Among, LWWR (LWWRRRWWL-NH 2) presented broad-spectrum antibacterial activity both in vitro and in vivo due to its multiple mechanisms and good stability. Meanwhile, the low drug resistance and toxicity of LWWR also suggested its potential for clinical application. The findings of this study will provide some inspiration for the design and development of potential antibacterial agents, and contribute to the elimination of bacterial infections worldwide as soon as possible. [Display omitted] [ABSTRACT FROM AUTHOR]

The nonselective membrane disruption of antimicrobial peptides (AMPs) helps in combating the antibacterial resistance. But their overall positive charges lead to undesirable hemolysis and toxicity toward normal living cells, as well as the rapid clearance from blood circulation. In consequence, developing smart AMPs to optimize the antimicrobial outcomes is highly urgent. Relying on the local acidity of microbial infection sites, in this work, we designed an acidity-triggered charge reversal nanotherapeutics with adaptable geometrical morphology for bacterial targeting and optimized therapy. C 16 -A 3 K 4 -CONH 2 was proposed and the ε-amino groups in lysine residues were acylated by dimethylmaleic amide (DMA), enabling the generated C 16 -A 3 K 4 (DMA)-CONH 2 to self-assemble into negatively charged spherical nanostructure, which relieved the protein adsorption and prolonged blood circulation in vivo. After the access of C 16 -A 3 K 4 (DMA)-CONH 2 into the microbial infection sites, acid-sensitive β-carboxylic amide would hydrolyze to regenerate the positive C 16 -A 3 K 4 -CONH 2 to destabilize the negatively charged bacterial membrane. In the meanwhile, attractively, the self-assembled spherical nanoparticle transformed to rod-like nanostructure, which was in favor of the efficient binding with bacterial membranes due to the larger contact area. Our results showed that the acid-activated AMP nanotherapeutics exhibited strong and broad-spectrum antimicrobial activities against Yeast, Gram-positive Staphylococcus aureus , Gram-negative Escherichia coli , and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, the biocompatible lipopeptide nanotherapeutics dramatically improved the dermapostasis caused by bacterial infection. The strategy of merging pathology-activated therapeutic function and morphological adaptation to augment therapeutic outcomes shows the great potential for bacterial inhibition. The overall positive charges of antimicrobial peptides (AMPs) lead to undesirable hemolysis and nonselective toxicity, as well as the rapid clearance from blood circulation. Infection-activated lipopeptide nanotherapeutics with adaptable geometrical morphology were developed to address these issues. The self-assembled lipopeptide was pre-decorated to reverse the positive charge to reduce the hemolysis and nonselective cytotoxicity. After accessing the acidic infection sites, the nanotherapeutics recovered the positive charge to destabilize negatively charged bacterial membranes. Meanwhile, the morphology of self-assembled nanotherapeutics transformed from spherical nanoparticles to rod-like nanostructures in the lesion site, facilitating the improved association with bacterial membranes to boost the therapeutic efficiency. These results provide new design rationale for AMPs developed for bacterial inhibition. [Display omitted] [ABSTRACT FROM AUTHOR]

Dental biofilms, impacting around 80% of the global population, are a significant issue causing serious dental disorders like periodontitis, which has links to autoimmune diseases such as rheumatoid arthritis. Traditional biofilm management methods, including mechanical removal and chemical agents, often fail to completely eradicate biofilms, allowing oral infections to persist. Nanotechnology offers innovative solutions for medication delivery and biofilm disruption, presenting new opportunities for antimicrobial surfaces and healthcare equipment development. This paper explores advancements in nanotechnology-based strategies to combat dental biofilms, primarily formed by Lactobacillus species, Actinomyces species, and Streptococcus mutans , and examines the composition and characteristics of dental biofilms. The green synthesis of nanoparticles using plant-based ingredients demonstrates significant antibacterial activity against biofilm-associated pathogens. Additionally, the paper investigates the potential of various metal oxide-based nanoparticles, such as titanium, zinc, and silver, in dental treatments to inhibit biofilm formation and enhance oral health. The stages of dental biofilm formation are outlined, highlighting the risks of untreated biofilms, including systemic health implications. This review underscores the promise of nanodrugs in preventing dental biofilms and improving the efficacy of dental procedures. It delves into cutting-edge nanotechnological approaches, emphasizing the novel use of nanoparticles like gold, silver, and antimicrobial peptides, and their unique mechanisms for disrupting biofilm formation and enhancing dental treatments. The review also covers recent advancements in nanotechnology, offering innovative and more effective solutions for targeted dental care strategies, potentially revolutionizing the approach to managing dental biofilms and promoting better oral health outcomes. [Display omitted] • Nanotechnology offers innovative drug delivery system for targeted and controlled release of antimicrobials in the oral cavity. • Green synthesis nanoparticles prepared in the budget friendly way. • Optimized drug delivery systems and conducted clinical trials validated the efficacy and safety of these nanodrug approaches in dental care. [ABSTRACT FROM AUTHOR]

The threat of antibiotic resistance to the public's health is exacerbated by the emergence of multidrug resistant bacterial (MDR) strains and their biofilm. Antibiotics are unable to penetrate the thick biofilm matrix causing the indwelling bacterial cells to survive resulting into the origin of antimicrobial resistance (AMR). Thus, biofilms are responsible for causing many chronic infections such as dental plaque formation, cystic fibrosis, urinary tract infections (UTI), otitis media etc. Hence, there is an urgent need for alternate therapeutic strategies for preventing bacterial biofilm formation and fighting AMR. In this regard antimicrobial peptides (AMPs) that have broad-spectrum antibacterial action with significant specificity and low toxicity, are a great choice to combat AMR. Peptides derived from snake venom such as cathelicidins reflects a spectrum of biological actions including its antimicrobial potential. The present study focuses on screening and identifying AMPs having anti-biofilm properties. This includes natural cathelicidins found in snake venom as a potential antibacterial agent to combat AMR. Two biofilm forming proteins were identified viz. icaC protein of Staphylococcus aureus & bdlA protein of Pseudomonus aureginosa. AMPs were screened from DRAMP Database and snake venom cathelicidins were selected for further studies. The binding interaction of cathelicidins with the icaC and bdlA protein were investigated using molecular docking studies. Based on the interacting amino acid residues, antigenic determinants, peptide binding site and docking scores a performance scale was built to classify relevant snake venom cathelicidins according to their importance for further in vivo and in vitro antibiofilm investigations. [ABSTRACT FROM AUTHOR]

Antimicrobial peptide Pup2, due to high cost, shows restricted application value in food preservative, which may be improved by interacting with EGCG, characterized by good functional properties. This study aims to characterize a novel antimicrobial peptide-phenolic complex with activity against Staphylococcus aureus and investigate their interaction mechanism. Pup2 and Epigallocatechin-3-gallate (EGCG) exhibited synergistic effects, resulting in a 4-fold and 8-fold decrease in the minimum inhibitory concentration, respectively. Furthermore, the Pup2/EGCG showed a synergistic damaging effect on the bacterial cell wall and membranes. Multi-spectroscopic analyses, which included UV, fluorescence, FTIR, and Raman spectroscopy, showed that Pup2 and EGCG were non-covalently bound through hydrophobic interactions predominantly and assisted by hydrogen bonding. These interactions led to changes in the amino acid microenvironment of Pup2 and alterations in its secondary structure, with the α- helix content increasing from 3% to 26%. DSC similarly confirmed the occurrence of interactions and increased peptide stability. Additionally, molecular simulations further demonstrated hydrophobic interaction and hydrogen bonding were the main binding forces between Pup2 and EGCG, resulting in the formation of a stable complex. This study helps to elucidate the interaction mechanism between antimicrobial peptide Pup2 and EGCG at the molecular level, while highlights the potential application of this complex as a more economical and effective natural antimicrobial preservative. [Display omitted] • Antimicrobial peptide Pup2 and EGCG exhibited synergistic antimicrobial effect. • Pup2/EGCG inactivated Staphylococcus aureus due to cell membrane damage. • Pup2/EGCG complex is formed by hydrophobic interactions and hydrogen bonds. • Molecular dynamics simulation showed good binding stability of the Pup2-EGCG complex. [ABSTRACT FROM AUTHOR]

Research suggests that both tuberculosis (TB) and type 2 diabetes mellitus (T2DM) have an immuno-endocrine imbalance characterized by dysregulated proinflammatory molecules and hormone levels (high cortisol/DHEA ratio), impeding an effective immune response against Mycobacterium tuberculosis (Mtb) driven by cytokines, antimicrobial peptides (AMPs), and androgens like DHEA. Insulin, sulfonylurea derivatives, and metformin are commonly used glucose-lowering drugs in patients suffering from TB and T2DM. For this comorbidity, metformin is an attractive target to restore the immunoendocrine mechanisms dysregulated against Mtb. This study aimed to assess whether metformin influences cortisol and DHEA synthesis in adrenal cells and if these hormones influence the expression of proinflammatory cytokines and AMPs in Mtb -infected macrophages. Our results suggest that metformin may enhance DHEA synthesis while maintaining cortisol homeostasis. In addition, supernatants from metformin-treated adrenal cells decreased mycobacterial loads in macrophages, which related to rising proinflammatory cytokines and AMP expression (HBD-2 and 3). Intriguingly, we find that HBD-3 and LL-37 can modulate steroid synthesis in adrenal cells with diminished levels of cortisol and DHEA, highlighting the importance of crosstalk communication between adrenal hormones and these effectors of innate immunity. We suggest that metformin's effects can promote innate immunity against Mtb straight or through modulation of corticosteroid hormones. [ABSTRACT FROM AUTHOR]

The initialization of the gingival crevicular barrier epithelium facing the exposed implant surface is reported to take 1--2 weeks, and peri-implant inflammation mediated by bacterial infection has been an increasing concern. In this study, we developed a novel composite coating containing graphene oxide (GO) and the antimicrobial peptide (AMP) Nal-P-113 on smooth titanium surface, and then investigated the antibacterial properties and cytocompatibility of the coating. The results showed that Nal-P-113 exhibited a slow and continuous drug release in vitro from the composite coating. The Nal-P-113-loaded GO coating demonstrated excellent antibacterial properties against both Gram-positive Streptococcus mutans (S. mutans) and Gram-negative Porphyromonas gingivalis (P. gingivalis), without no obvious cytotoxicity to human gingival fibroblast (HGF) cells. The Nal-P-113-loaded GO coating need further optimization for anti-infective and wound healing promoting purpose of peri-implant tissues. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are considered to be powerful weapons in the fight against traditional antibiotic resistance due to their unique membrane-disruptive mechanism. The combination of traditional and classical hydrophobic tryptophan (W) residues and hydrophilic charged arginine (R) residues is considered as the first choice for the minimalist design of AMPs due to its potent performance in antibacterial activity. However, some W- and R-rich AMPs that are not rationally designed and contain excessive repeats of W and R residues may cause severe cytotoxicity and hemolysis. To address this issue, we designed the (WRX) n (where X = hydrophilic uncharged amino residues; n = number of repeat units) series engineered peptides with high cell selectivity by introducing hydrophilic uncharged threonine (T), serine (S), glutamine (Q) or asparagine (N) residues into the minimalist design of W- and R-rich AMPs. The results showed that the introduction of these hydrophilic uncharged amino residues, especially T residues, significantly improved the cell selectivity of the W- and R-rich engineered peptides. Among (WRX) n series engineered peptides, T6 presents a mixture structure of β-turn and α-helix. It has broad spectrum and potent antibacterial activity (no activity against probiotics), good biocompatibility, high selectivity index, strong tolerance (physiological salts, serum acid, alkali, and heat conditions), rapid and efficient time-kill kinetics, and no tendency of resistance. Studies on antibacterial mechanism show that T6 exert antibacterial activity mainly by disrupting bacterial cell membrane and inducing the accumulation of reactive oxygen species in bacterial cells. Furthermore, T6 exhibited potent antibacterial and antiinflammatory capabilities in vivo in a mouse peritonitis-sepsis model infected with Escherichia coli. In conclusion, our study confirms an effective strategy for the minimalist design of highly cell selective W- and R-rich AMPs by introducing hydrophilic uncharged T residues, which may trigger widespread attention to hydrophilic uncharged amino acid residues, including T residues, and provide new insights into the design of peptide-based antibacterial biomaterials. We have introduced hydrophilic uncharged T, S, Q or N residues into the minimalist design of W- and R-rich engineered peptides and found that the introduction of these hydrophilic uncharged amino residues, especially the T residues, can significantly improve the cell selectivity of W- and R-rich engineered peptides. The target compound T6 showed potent antibacterial activity, high cell selectivity, strong tolerance, good in vivo efficacy and killed bacteria through multiple mechanisms mainly membrane-disruptive. These findings may spark widespread interest in hydrophilic uncharged amino acid residues, and provide new insights into the design of peptide-based antimicrobial biomaterials. [Display omitted] [ABSTRACT FROM AUTHOR]

The biggest application bottleneck of antimicrobial peptides (AMPs) is the low oral bioavailability caused by the poor stability of digestive enzymes in the gastrointestinal tract. However, the research methods and evaluation criteria of available studies about anti-proteolytic strategies are not uniform and far from the actual environment in vivo. Here, we developed a research system and evaluation criteria for proteolytic resistance and systematically evaluated the effectiveness of different strategies for improving the protease stability of AMPs on the same platform for the first time. After a comprehensive analysis, Dab modification is identified as the most effective strategy to improve the trypsin stability of AMPs. By further modulating the proteolytic resistance optimization motif (DabW) n , U1-2WD is obtained with ideal stability and antimicrobial properties in vivo and in vitro. Notably, U1-2WD has a unique antibacterial mechanism, which forms amorphous aggregates in the bacteria environment to trigger the agglutination of bacterial cells to prevent bacterial escape. It then kills bacteria by disrupting bacterial membranes and inhibiting bacterial energy metabolism. Overall, our work has led to a new understanding of the effectiveness of proteolytic resistance strategies and accelerated the development of anti-proteolytic AMPs to combat multidrug-resistant bacterial infections. We developed research system and evaluation criteria for proteolytic resistance and systematically evaluated the effectiveness of different strategies for improving protease stability of AMPs on the same platform for the first time. we found effective strategies to resist trypsin hydrolysis: modification with backbone (β-Arg), D-enantiomer (D-Arg) and L-2,4-diaminobutanoic acid (Dab). Further, the proteolytic resistance optimization motif (DabW) n was designed. When n=3, derivative U1-2WD was obtained with desirable stability and antimicrobial properties in vivo and in vitro. Notably, U1-2WD has a unique antibacterial mechanism, which can self-aggregate into amorphous aggregates in the bacteria environment to mediate the agglutination and sedimentation of bacterial cells to prevent bacterial escape, and then kill bacteria by destroying bacterial membranes and inhibiting bacterial energy metabolism. [Display omitted] [ABSTRACT FROM AUTHOR]

The growing microbial resistance to antibiotics is a global public concern, which creates serious needs for newer antimicrobial agents. Antimicrobial peptides (AMPs) are increasingly exploited in drug development as therapeutic candidates. Here, we aimed to design and characterize a novel peptide with broad spectrum antimicrobial activity. Hybridization and sequence modification approaches were used to design the novel peptide, named HAZ, aiming at optimizing the physicochemical parameters involved in antimicrobial activity. Peptide activities were assessed alone or combined with different selected antibiotics against various sensitive and drug-resistant bacterial strains. In addition, the hemolysis and the cytotoxic activities of HAZ peptide were evaluated on human red blood cells and epithelial adenocarcinoma cells (A549), respectively. HAZ peptide was sequentially modified to result in favored physicochemical parameters (helicity 95.24 %, hydrophobic ratio 47 %, and net charge of 8 +). Functional assessment of HAZ revealed significant antimicrobial activity, with MIC values of 15 – 20 µM against tested bacterial strains. It also exhibited biofilm eradication activity at slightly higher concentrations. HAZ-antibiotics combinations exhibited a synergistic action mode that led to dramatic decrease in the MIC values for both HAZ peptide and the antibiotic. Such efficacy was accompanied with minimal hemolytic toxicity on human erythrocytes. Importantly, HAZ displayed promising anticancer activity against human lung cancer cells. Rationally-designed antimicrobial peptides offer promising alternatives to the current antibiotics for management of infectious diseases. HAZ peptide is a broad-spectrum AMP, and a promising candidate for antimicrobial and anticancer drug development. [ABSTRACT FROM AUTHOR]

Bacterial infection and local growth factor deficiency are two of the major causes of the nonunion of diabetic wounds. Antimicrobial peptides (AMPs) are believed to be alternatives to antibiotics against drug-resistant bacterial infections. 8-Bromoadenosine-3', 5'-cyclic monophosphate (8Br-cAMP) can promote cells to secrete growth factors and accelerate cell proliferation. In the present study, we constructed a hydrogel with antimicrobial peptide Jelleine-1 (J-1) and 8Br-cAMP without any other gelators or chemical crosslinking agents. The hydrogel was proved to promote the secretion of transforming growth factor-β (TGF-β) and vascular endothelial growth factor-A (VEGFA) in vitro and in vivo. Notably, it exhibited potent potential for wound healing in methicillin-resistant Staphylococcus aureus (MRSA) infected diabetic wounds. This would be attributed to the retention of AMPs and 8Br-cAMP on the wound site by the hydrogel system. In addition, the hydrogel also showed good biodegradability, proper stability, and good biocompatibility. This study would shed light on the development of carrier-free and multifunctional hydrogel for wound healing. Bacterial infection and local growth factor deficiency are two of the major causes for the nonunion of refractory wounds. In the present study, an injectable carrier-free hydrogel was constructed of a natural antimicrobial peptide J-1 and 8Br-cAMP by eco-friendly physical crosslinking without any other gelators or chemical crosslinking agents. The hydrogel exhibited excellent antimicrobial activity and was proved to promote the secretion of TGF-β and VEGFA in vitro and in vivo. Correspondingly, the hydrogel showed exceptionally wound healing effects in the wound model of MRSA infected diabetic rats. This study would provide an alternative strategy or a potential hydrogel dressing for the treatment of chronic or refractory wounds. [Display omitted] [ABSTRACT FROM AUTHOR]

Focal bacterial infections are often difficult to treat due to the rapid emergence of antibiotic-resistant bacteria, high risk of relapse, and severe inflammation at local lesions. To address multidrug-resistant skin and soft tissue infections, a bacteria-absorbing sponge was prepared to involve a "trap-and-kill" mechanism. The system describes a guanidinium-rich lipopeptide functionalized lyotropic liquid-crystalline hydrogel with bicontinuous cubic networks. Amphiphilic lipopeptides can be spontaneously anchored to the lipid-water interface, exposing their bacterial targeting sequences to enhance antibacterial trapping/killing activity. Computational simulations supported our structural predictions, and the sponge was confirmed to successfully remove ∼98.8% of the bacteria in the medium. Release and degradation behavior studies indicated that the bacteria-absorbing sponge could degrade, mediate enzyme-responsive lipopeptide release, or generate ∼200 nm lipopeptide nanoparticles with environmental erosion. This implies that the sponge can effectively capture and isolate high concentrations of bacteria at the infected site and then sustainably release antimicrobial lipopeptides into deep tissues for the eradication of residual bacteria. In the animal experiment, we found that the antibacterial performance of the bacterial-absorbing sponge was significant, which demonstrated not only a long-term inhibition effect to disinfect and avoid bacterial rebound, but also a unique advantage to protect tissue from bacterial attack. Host defense peptides/peptidomimetics (HDPs) have shown potential for the elimination of focal bacterial infections, but the application of their topical formulations suffers from time-consuming preparation processes, indistinctive toxicity reduction effects, and inefficient bacterial capture ability. To explore new avenues for the development of easily prepared, low-toxicity and high-efficiency topical antimicrobials, a guanidinium-rich lipopeptide was encapsulated in a lyotropic liquid-crystalline hydrogel (denoted as "bacteria-absorbing sponge") to achieve complementary superiorities. The superior characteristic of the bacteria-absorbing sponge involves a "trap-and-kill" mechanism, which undergoes not only a long-term inhibition effect to disinfect and avoid bacterial rebound, but also effective bacterial capture and isolating action to confine bacterial diffusion and protect tissues from bacterial attack. [Display omitted] [ABSTRACT FROM AUTHOR]

An infecting and propagating parasite relies on its innate defense system to evade the host's immune response and to survive challenges from commensal bacteria. More so for the nematode Anisakis , a marine parasite that during its life cycle encounters both vertebrate and invertebrate hosts and their highly diverse microbiotas. Although much is still unknown about how the nematode mitigates the effects of these microbiota, its antimicrobial peptides likely play an important role in its survival. We identified anisaxins, the first cecropin-like helical antimicrobial peptides originating from a marine parasite, by mining available genomic and transcriptomic data for Anisakis spp. These peptides are potent bactericidal agents in vitro , selectively active against Gram-negative bacteria, including multi-drug resistant strains, at sub-micromolar concentrations. Their interaction with bacterial membranes was confirmed by solid state NMR (ssNMR) and is highly dependent on the peptide concentration as well as peptide to lipid ratio, as evidenced by molecular dynamics (MD) simulations. MD results indicated that an initial step in the membranolytic mode of action involves membrane bulging and lipid extraction; a novel mechanism which may underline the peptides' potency. Subsequent steps include membrane permeabilization leading to leakage of molecules and eventually cell death, but without visible macroscopic damage, as shown by atomic force microscopy and flow cytometry. This membranolytic antibacterial activity does not translate to cytotoxicity towards human peripheral blood mononuclear cells (HPBMCs), which was minimal at well above bactericidal concentrations, making anisaxins promising candidates for further drug development. Witnessing the rapid spread of antibiotic resistance resulting in millions of infected and dozens of thousands dying worldwide every year, we identified anisaxins, antimicrobial peptides (AMPs) from marine parasites, Anisakis spp., with potent bactericidal activity and selectivity towards multi-drug resistant Gram-negative bacteria. Anisaxins are membrane-active peptides, whose activity, very sensitive to local peptide concentrations, involves membrane bulging and lipid extraction, leading to membrane permeabilization and bacterial cell death. At the same time, their toxicity towards host cells is negligible, which is often not the case for membrane-active AMPs, therefore making them suitable drug candidates. Membrane bulging and lipid extraction are novel concepts that broaden our understanding of peptide interactions with bacterial functional structures, essential for future design of such biomaterials. [Display omitted] [ABSTRACT FROM AUTHOR]

As an important order among insects, featuring incredible diversity, Coleopterans are increasingly the subject of immunity research. They are not vectors of human and animal diseases, but their impact on plant communities and plant-based food sources, mainly as pests (forest, agricultural, and storage), is significant. Insect immunity research focuses on the mechanisms required for host defense against a wide array of pathogens. The role of the fat body, hemocytes, the formation of antimicrobial peptides, as well as signaling pathways against infection are essential to insect immunity. Innate immune mechanisms in beetles are closely related to their pathology and the hosts' responses to infectious agents (viruses, bacteria, fungi, microsporidia). Most of the established mechanisms of beetle innate immunity mainly come from model organisms such as Tenebrio molitor, Tribolium castaneum, and Leptinotarsa decemlineata. With the advent of modern and environmentally friendly approaches to pest control, more and more issues related to their reactions to pathogenic infections are becoming key. The current review presents a summary of studied defense mechanisms in Coleoptera and data on insect immunity, established in more than 50 beetle species. [ABSTRACT FROM AUTHOR]

Background: Innate immunity plays an important role in deciding the severity of coronavirus disease 2019 (COVID-19) and disease outcomes. Defensins are antimicrobial peptides that are produced by epithelial cells in mucosal locations and play a key role in innate immunity. Understanding COVID-19 mucosal agents and their role in disease severity is critical for developing therapeutic options and identification of prognostic markers for COVID-19. Objective: In this study, we aimed to determine the role of b-defensin-1 in patients with COVID-19 and compare it with that of the control group, as well as to look into the link between b-defensin-1 and oral hygiene and disease severity. Methods: This case-control study included 50 patients with COVID-19 and 35 controls of similar ages and sexes. From November 2020 to January 2021, the patients were admitted to Baghdad Teaching Hospital/Medical City. The simplified oral hygiene index was used to determine oral hygiene status. Blood samples were obtained from all subjects (patients and controls), and the serum levels of bdefensin-1 were measured using enzyme-linked immunosorbent assay (ELISA). Results: Findings showed a non-significant reduction (P < 0.05) in the b-defensin-1 level among patients compared with that of the controls. In addition, patients with severe disease had a significantly lower level of b-defensin-1 than those with mild disease. There were no significant variations in the levels of b-defensin-1 between patients with good oral hygiene and those with poor oral hygiene (P < 0.05). Conclusions: The reduction in b-defensin-1 levels indicates an abnormal immune response in these patients and may require a new treatment option for this condition in the future. Furthermore, in patients with severe disease, a considerable drop in b-defensin-1 might be used as an indicator of illness severity. [ABSTRACT FROM AUTHOR]

Niclosamide (NIC) is a commonly used insecticide and molluscicide in the prevention and treatment of parasitic diseases in fish. The utilization of NIC has the potential to disrupt the microbial community present on the mucosal tissue of fish, leading to localized inflammatory responses. The objective of this study was to evaluate the impact of NIC on the immune system and bacterial populations within the gill and gut of Mylopharyngodon piceus. Fish were subjected to varying concentrations of NIC, including a control group (0 μg/L), a low NIC group (15% 96 h LC50, LNG, 9.8 μg/L), and a high NIC group (80% 96 h LC50, HNG, 52.5 μg/L). Gill and gut samples were collected 28 days post-exposure for analysis. The findings revealed that the 96-h LC 50 for NIC was determined to be 65.7 μg/L, and histopathological examination demonstrated that exposure to NIC resulted in gill filament subepithelial edema, exfoliation, degeneration, and a decrease in gill filament length. Furthermore, the gut exhibited apical enterocyte degeneration and leucocyte infiltration following NIC exposure. Additionally, NIC exposure led to a significant elevation in the levels of immunoglobulin M (IgM), complement component 3 (C3), and complement component 4 (C4) in both gill and gut tissues. Moreover, the activity of lysozyme (LYZ) was enhanced in the gill, while the activities of peroxidase (POD) and immunoglobulin T (IgT) were increased in gut tissue. The exposure to NIC resulted in enhanced mRNA expression of c3 , c9 , tnfα , il6 , il8 , and il11 in the gill tissue, while decreasing c3 and il8 expression in the gut tissue. Furthermore, the natural resistance-associated macrophage protein (nramp) mRNA increased, and liver-expressed antimicrobial peptide 2 (leap2) mRNA decreased in gill and gut tissues. And hepcidin (hepc) mRNA levels rose in gill but fell in gut tissue. NIC exposure also led to a decrease in gill bacterial richness and diversity, which significantly differed from the control group, although this separation was not significant in the gut tissue. In conclusion, the administration of NIC resulted in alterations in both the immune response and mucosal microbiota of fish. Furthermore, it was noted that gills displayed a heightened vulnerability to sublethal effects of NIC in comparison to gut tissues. • Niclosamide subacute exposure alters the immune response of the gill and gut in black carp. • The gill and gut microbiota composition in black carp changed significantly after niclosamide subacute exposure. • Gills displayed a heightened vulnerability to sublethal effects of NIC in comparison to gut tissues. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a major threat worldwide especially when it comes to nosocomial infections caused by ESKAPE bacteria. These pathogens exhibit a remarkable capacity to develop resistance to antimicrobial treatments. Probiotics are receiving considerable attention as potential antimicrobial therapies that are safe, and very effective. The objective of this study is to identify a possible treatment using antimicrobial peptides (AMPs) derived from probiotics. The primary objective is to comprehend the interplay between AMPs and the virulence proteins produced by ESKAPE pathogens that are linked with biofilms. We subjected the 12 peptides found in our earlier investigation to a comprehensive screening approach targeting the virulence proteins of ESKAPE infections by applying shape complementarity concepts and chose the docked complexes with the lowest energy score. The screening process involved assessing binding affinity and interactions with active residues using sophisticated computational tools such as HPEPDOCK, ClusPro 2.0, and AutoDock Vina. The AMP designated as plsa_07 was selected for subsequent examination and validated using molecular dynamic simulations. The in vitro assay demonstrated the antibacterial and antibiofilm properties of AMP plsa_07, with a minimal inhibitory concentration ranging from 1 to 4 μg/ml. The AMP plsa_07 demonstrated biofilm inhibition and eradication action against various bacteria, including E. faecium , S.aureus , K. pneumoniae , A. baumannii , and P. aeruginosa , with a range of effectiveness between 17% and 70%. This study establishes a fundamental foundation for clinical research on the possible application of therapeutic peptides produced from probiotics to address the increasing problem of drug-resistant infections. [ABSTRACT FROM AUTHOR]

As amphibians undergo thyroid hormone (TH)-dependent metamorphosis from an aquatic tadpole to the terrestrial frog, their innate immune system must adapt to the new environment. Skin is a primary line of defense, yet this organ undergoes extensive remodelling during metamorphosis and how it responds to TH is poorly understood. Temperature modulation, which regulates metamorphic timing, is a unique way to uncover early TH-induced transcriptomic events. Metamorphosis of premetamorphic tadpoles is induced by exogenous TH administration at 24 °C but is paused at 5 °C. However, at 5 °C a "molecular memory" of TH exposure is retained that results in an accelerated metamorphosis upon shifting to 24 °C. We used RNA-sequencing to identify changes in Rana (Lithobates) catesbeiana back skin gene expression during natural and TH-induced metamorphosis. During natural metamorphosis, significant differential expression (DE) was observed in >6500 transcripts including classic TH-responsive transcripts (thrb and thibz), heat shock proteins, and innate immune system components: keratins, mucins, and antimicrobial peptides (AMPs). Premetamorphic tadpoles maintained at 5 °C showed 83 DE transcripts within 48 h after TH administration, including thibz which has previously been identified as a molecular memory component in other tissues. Over 3600 DE transcripts were detected in TH-treated tadpoles at 24 °C or when tadpoles held at 5 °C were shifted to 24 °C. Gene ontology (GO) terms related to transcription, RNA metabolic processes, and translation were enriched in both datasets and immune related GO terms were observed in the temperature-modulated experiment. Our findings have implications on survival as climate change affects amphibia worldwide. [Display omitted] • The bullfrog back skin (BS) is a critical innate immune system component. • It undergoes thyroid hormone (TH)-induced remodelling during metamorphosis. • TH induced changes are uncoupled from initiation at 5 °C (molecular memory). • Transcriptome profiles reveal new molecular memory components. • Bioinformatics analyses identified novel putative antimicrobial peptides (AMPs). [ABSTRACT FROM AUTHOR]

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin , lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A , a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts. [Display omitted] • Nicotine intake increased the abundance of symbiotic gut bacterium BsNLG8, leading to a stronger bacteriostatic effect. • Nicotine stimulated the differential expression of immune genes, with Defensin A exhibiting a significant response. • Silencing of Defensin A in N. lugens reduced survival, enhanced nicotine sensitivity and decreased the abundance of BsNLG8. • Reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine-induced stress was unveiled. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are a type of small protein that is part of the innate immune system and is widely distributed in marine organisms. Seafood by-products and discards are a good source of AMPs. The AMPs isolated and extracted from marine byproducts have been identified to possess various biological activities, including antibacterial, anticancer, immunomodulatory, and anti-inflammatory activities. This study provides a comprehensive overview of research progress on extracting AMPs from by-products and discards generated during seafood processing. It includes an analysis of different types of AMPs, reviews extraction methodologies, and evaluates current status alongside future perspectives for their application. By exploring the potential of AMPs derived from seafood by-products and discards, this review aimed to promote sustainable seafood utilization while addressing environmental concerns. In conclusion, the objective of this research is to provide support for the efficient management of seafood by-products and discards, leading to the production of value-added products. [Display omitted] • Seafood by-products/discards are a high-quality source of bioactive peptides. • The development of bioactive peptides is of great significance. • The ability to obtain antimicrobial peptides still needs to be improved. • Provides a reference for the high-value utilization of seafood by-products/wastes. [ABSTRACT FROM AUTHOR]

This study aimed to purify and characterize a novel antibacterial substance produced by Lactiplantibacillus plantarum CS3 and explored its antibacterial mechanism. Antimicrobial substances were isolated and purified by ultrafiltration, extraction, and gel filtration chromatography. The purified substance was identified by LC/MS as the WRWLRKL heptapeptide (1057.29 Da). The minimum inhibitory concentrations of the crude extract of antimicrobial peptides (CS3–F2) against Staphylococcus hominis and Staphylococcus capitis were 1.25 mg/ml and 1 mg/ml, respectively. The crude extract directly affected the cell wall and membrane, inhibited biofilm formation, caused leakage of cell contents, and directly bound to genomic DNA, affecting the respiratory metabolism of spoilage bacteria, blocking normal binding of enzymes and receptors, and ultimately leaded to cell death. Furthermore, the addition of L. plantarum CS3 could improve the quality and flavor characteristics of soy sauce. • Isolation and purification antibacterial substances from the CFS of L. plantarum. • WRWLRKL was detected as a new antimicrobial. • Antibacterial substances killed bacteria by disrupting the integrity of the cells. • L. plantarum CS3 improved the acid and ester content of soy sauce. [ABSTRACT FROM AUTHOR]

Background: Many active peptides have been found in frog skin secretions. In this paper, our research focused on Pelophylax nigromaculatus and found a broad-spectrum antimicrobial peptide Nigrocin-PN based on the molecular cloning technique. Thereafter, the "Rana box" function was briefly studied by two mutated peptides (Nigrocin-M1 and Nigrocin-M2). Furthermore, in vitro and in vivo assays were used to characterize the peptide's biofunctions, and the peptide's function in treating multidrug-resistant pathogens was also studied. Results: Nigrocin-PN not only displayed potent antimicrobial abilities in vitro but also significantly ameliorated pulmonary inflammation induced by Klebsiella pneumoniae in vivo. By comparing, leucine-substituted analogue Nigrocin-M1 only displayed bactericidal abilities towards gram-positive bacteria, while the shorter analogue Nigrocin-M2 lost this function. More strikingly, Nigrocin-PN exhibited synergistic effects with commonly used antibiotics; in vitro evolution experiments revealed that coadministration between Nigrocin-PN and ampicillin could delay Staphylococcus aureus antibiotic resistance acquisition. Kinetics and morphology studies indicate that antibacterial mechanisms involved membrane destruction. Furthermore, toxicities and anticancer abilities of these peptides were also studied; compared to two analogues, Nigrocin-PN showed mild haemolytic activity and indistinctive cytotoxicity towards normal cell lines HMEC-1 and HaCaT. Conclusions: A broad-spectrum antimicrobial peptide Nigrocin-PN was discovered from the skin secretion of Pelophylax nigromaculatus. Structurally, "Rana box" played a crucial role in reducing toxicities without compromising antibacterial abilities, and Nigrocin-PN could be a desired therapeutic candidate. Highlights: • For AMPs, disulphide bond can affect their biofunction and cytotoxicity. • Frog skin secretion is a reservoir to delve valuable peptides. • AMPs-antibiotics coadministration could be a strategy to delay drug resistance. [ABSTRACT FROM AUTHOR]

The immune system is an extremely complex biological network that plays a crucial role in the hemostasis of periapical tissue, pathogenesis of apical periodontitis (AP), and periapical tissue healing. The successful elimination of microbial infections remains a significant challenge, mostly because of the ever-growing development of antimicrobial-resistant pathogens. The bacterial endurance in the root canal system contributes to features ranging from altered posttreatment healing to exacerbation of chronic periradicular immune response, which compromise the outcome of endodontic treatment. A highly effective strategy for combating infectious diseases and the associated inflammation-mediated tissue damage is to modulate the host immune response in conjunction with antimicrobial therapy. There are several medications currently used in endodontic treatment; however, they suffer various levels of microbial resistance and do not deliver all the required characteristics to simultaneously address both intracanal bacteria and periapical inflammation. The interaction of antimicrobial agents with the immune system can impact its function, leading to immune-suppressive or immune-stimulatory effects. The group of nonconventional antimicrobial medications, such as antimicrobial peptides, propolis, and nanomaterials, are agents that provide strong antimicrobial effectiveness and concomitant immunomodulatory and/or reparative effect without any host tissue damages. In this review, we provide an overview of local immune modulation in AP and a comprehensive review of the immunomodulatory effect of antimicrobial intracanal medications applied in endodontics with specific emphasis on the antimicrobial nanomaterial-based approaches that provide immunomodulatory potential for successful clinical deployment in endodontics. [ABSTRACT FROM AUTHOR]

Membrane active antimicrobial peptide mimics have been considered as promising alternatives to antibiotics, which interact with bacterial cell membranes to combat bacteria and avoid the emergence of multidrug-resistant bacteria. Herein, a series of star-shaped and membrane-active cationic polyetheramides derived from amino acids, were synthesized via condensation of amino acids and polyetheamine (T403). The antibacterial and anti-biofilm activitives as well as the biocompatibility of these amino acids derived polyetheramides (AAPEAs) were investigated in detail. The star-shaped AAPEAs showed high-efficient and broad-spectrum antibacterial activity against the E nterococcus faecium , S taphylococcus aureus , K lebsiella pneumoniae , A cinetobacter baumannii , P seudomonas aeruginosa , and E nterobacter species (ESKAPE) pathogens. In addition, the antibacterial activity was significantly affected by the type of amino acid. L-Trp-T403, which was obtained from L-tryptophan and polyetheramine, exhibited the best antibacterial activity with the minimum inhibitory concentration (MIC) of 1 µg/mL against methicillin-resistant S. aureus (MRSA). Time-kill kinetics and multi-passage resistance tests experiments indicated that L-Trp-T403 could rapidly kill bacteria within 1 h. This compound also showed potent antibacterial activity against bacteria over many passages. Moreover, the AAPEAs exhibited outstanding stability and long-term antibacterial activity in complex mammalian body fluids, as well as good biocompatibility, low hemolytic activity, slight toxicity for mammalian cell (L929) and low in vivo toxicity. The antibacterial activity of L-Trp-T403 was found to be based on the disruption of bacterial membranes, which leads to the leakage of the internal cytoplasm. The AAPEAs possessed high antibacterial and anti-biofilm activity, thus, they are promising to be used as long-term and biofilm-disrupting antimicrobial agents. The growing epidemic of MDR-bacteria is becoming a severe public health threat. Here, a series of amino acids derived polyetheramides (AAPEAs) with a star-shaped polyether amide scaffold was synthesized. The star-shaped AAPEAs displayed broad-spectrum antibacterial activity against Gram-positive, Gram-negative bacteria and drug-resistant bacteria MRSA. Notably, the star-shaped AAPEAs were stable under plasma conditions and showed outstanding stability and long-term antibacterial activity in various complex mammalian fluids. Moreover, these star-shaped AAPEAs not only inhibited the formation of biofilms but also disrupted the established biofilms. Furthermore, the membrane-active AAPEAs eradicated bacteria via the fast membrane lytic mechanism, thus plausibly overcoming the MDR effect. These results demonstrate that membrane-active AAPEAs can serve as emerging long-term and biofilm-disrupting antimicrobial agents to treat biofilm-related infections. [Display omitted] [ABSTRACT FROM AUTHOR]