Phage-displayed heptapeptide sequence conjugation significantly improves the specific targeting ability of antimicrobial peptides against Staphylococcus aureus.

Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

The effects of submicron-textured surface topography on antibiotic efficacy against biofilms.

Submicron-textured surfaces have been a promising approach to mitigate biofilm development and control microbial infection. However, the use of the single surface texturing approach is still far from ideal for achieving complete control of microbial infections on implanted biomedical devices. The use of a surface topographic modification that might improve the utility of standard antibiotic therapy could alleviate the complications of biofilms on devices. In this study, we characterized the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa on smooth and submicron-textured polyurethane surfaces after 1, 2, 3, and 7 days, and measured the efficacy of common antibiotics against these biofilms. Results show that the submicron-textured surfaces significantly reduced biofilm formation and growth, and that the efficacy of antibiotics against biofilms grown on textured surfaces was improved compared with smooth surfaces. The antibiotic efficacy appears to be related to the degree of biofilm development. At early time points in biofilm formation, antibiotic treatment reveals reasonably good antibiotic efficacy against biofilms on both smooth and textured surfaces, but as biofilms mature, the efficacy of antibiotics drops dramatically on smooth surfaces, with lesser decreases seen for the textured surfaces. The results demonstrate that surface texturing with submicron patterns is able to improve the use of standard antibiotic therapy to treat device-centered biofilms by slowing the development of the biofilm, thereby offering less resistance to antibiotic delivery to the bacteria within the biofilm community.

Comprehensive Review of Olea europaea: A Holistic Exploration into Its Botanical Marvels, Phytochemical Riches, Therapeutic Potentials, and Safety Profile.

Human health is now inextricably linked to lifestyle choices, which can either protect or predispose people to serious illnesses. The Mediterranean diet, characterized by the consumption of various medicinal plants and their byproducts, plays a significant role in protecting against ailments such as oxidative stress, cancer, and diabetes. To uncover the secrets of this natural treasure, this review seeks to consolidate diverse data concerning the pharmacology, toxicology, phytochemistry, and botany of Olea europaea L. (O. europaea). Its aim is to explore the potential therapeutic applications and propose avenues for future research. Through web literature searches (using Google Scholar, PubMed, Web of Science, and Scopus), all information currently available on O. europaea was acquired. Worldwide, ethnomedical usage of O. europaea has been reported, indicating its effectiveness in treating a range of illnesses. Phytochemical studies have identified a range of compounds, including flavanones, iridoids, secoiridoids, flavonoids, triterpenes, biophenols, benzoic acid derivatives, among others. These components exhibit diverse pharmacological activities both in vitro and in vivo, such as antidiabetic, antibacterial, antifungal, antioxidant, anticancer, and wound-healing properties. O. europaea serves as a valuable source of conventional medicine for treating various conditions. The findings from pharmacological and phytochemical investigations presented in this review enhance our understanding of its therapeutic potential and support its potential future use in modern medicine.

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes.

Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host's defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.

Molecular characterization, immune functions and DNA protective effects of peroxiredoxin-1 gene in Antheraea pernyi.

Peroxiredoxins are antioxidant proteins that detoxify peroxynitrite, hydrogen peroxide, and organic hydroperoxides, impacting various physiological processes such as immune responses, apoptosis, cellular homeostasis, and so on. In the present study, we identified and characterized peroxiredoxin 1 from Antheraea pernyi (thereafter designated as ApPrx-1) that encodes a predicted 195 amino acid residue protein with a 21.8 kDa molecular weight. Quantitative real-time PCR analysis revealed that the mRNA level of ApPrx-1 was highest in the hemocyte, fat body, and midgut. Immune-challenged larval fat bodies and hemocytes showed increased ApPrx-1 transcript. Moreover, ApPrx-1 expression was induced in hemocytes and the whole body of A. pernyi following exogenous H2O2 administration. A DNA cleavage assay performed using recombinant ApPrx-1 protein showed that rApPrx-1 protein manifests the ability to protect supercoiled DNA damage from oxidative stress. To test the rApPrx-1 protein antioxidant activity, the ability of the rApPrx-1 protein to remove H2O2 was assessed in vitro using rApPrx-1 protein and DTT, while BSA + DDT served as a control group. The results revealed that ApPrx-1 can efficiently remove H2O2 in vitro. In the loss of function analysis, we found that ApPrx-1 significantly increased the levels of H2O2 in ApPrx-1-depleted larvae compared to the control group. We also found a significantly lower survival rate in the larvae in which ApPrx-1 was knocked down. Interestingly, the antibacterial activity was significantly higher in the ApPrx-1 depleted larvae, compared to the control. Collectively, evidence strongly suggests that ApPrx-1 may regulate physiological activities and provides a reference for further studies to validate the utility of the key genes involved in reliving oxidative stress conditions and regulating the immune responses of insects.

Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients.

BACKGROUND: Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and increased susceptibility to infections. Recently, there is increased interest in the skin microbiome; therefore, we hypothesized that CI patients likely exhibit an abnormal profile of epidermal microbes because of their various underlying skin barrier defects. Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI. RESULTS: This case-control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing. CONCLUSIONS: Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.

Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections.

Lipocalin 2 (LCN2) plays a pivotal role in iron metabolism, particularly in the context of microbial infection resistance (e.g., viruses, bacteria, parasites, etc.). LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron, inducing immune cells to secrete various cytokines to enhance systemic immune responses, or recruiting neutrophils to infectious sites. The liver serves as the primary organ for LCN2 secretion during microbial infections. This review encapsulates recent advances in dynamic changes, clinical values, and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.

Identification of a novel DNA repair inhibitor using an in silico driven approach shows effective combinatorial activity with genotoxic agents against multidrug-resistant Escherichia coli.

Increasing antimicrobial drug resistance represents a global existential threat. Infection is a particular problem in immunocompromised individuals, such as patients undergoing cancer chemotherapy, due to the targeting of rapidly dividing cells by antineoplastic agents. We recently developed a strategy that targets bacterial nucleotide excision DNA repair (NER) to identify compounds that act as antimicrobial sensitizers specific for patients undergoing cancer chemotherapy. Building on this, we performed a virtual drug screening of a ~120,000 compound library against the key NER protein UvrA. From this, numerous target compounds were identified and of those a candidate compound, Bemcentinib (R428), showed a strong affinity toward UvrA. This NER protein possesses four ATPase sites in its dimeric state, and we found that Bemcentinib could inhibit UvrA's ATPase activity by ~90% and also impair its ability to bind DNA. As a result, Bemcentinib strongly diminishes NER's ability to repair DNA in vitro. To provide a measure of in vivo activity we discovered that the growth of Escherichia coli MG1655 was significantly inhibited when Bemcentinib was combined with the DNA damaging agent 4-NQO, which is analogous to UV. Using the clinically relevant DNA-damaging antineoplastic cisplatin in combination with Bemcentinib against the urological sepsis-causing E. coli strain EC958 caused complete growth inhibition. This study offers a novel approach for the potential development of new compounds for use as adjuvants in antineoplastic therapy.

ABCs begin with ZEB2.

Age-associated B cells (ABCs) are a stable subset of memory B lymphocytes that develop during microbial infections and in autoimmune diseases. Despite growing appreciation of their phenotypic and functional characteristics, the transcriptional networks involved in ABC fate commitment and maintenance have remained elusive. In their recent publication, Dai et al. tackle this problem, leveraging both mouse models and human diseases to reveal zinc finger E-box-binding homeobox 2 (ZEB2) as a key transcriptional regulator of ABC lineage specification. In aggregate, their results show that ZEB2, a member of the zinc finger E homeobox binding family, promotes ABC differentiation by repressing alternative differentiative fates and targeting genes important for ABC character and function. Moreover, their results strengthen the case for causal links between ABC fate and function in autoimmune pathologies.

Green and cost-effective biofabrication of copper oxide nanoparticles: Exploring antimicrobial and anticancer applications.

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as novel therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an innovative approach for future therapeutic interventions against cancer and microbial infections.

Photosensitised versus conventional infection control: the local fight continues.

The worsening problem of antimicrobial drug resistance requires a nuanced approach. Since the conventional drug pipeline is unlikely to be sufficient to avoid massive increases in mortality by the mid-twenty-first century, other methods of antisepsis will be required. These might be used either in place of (allowing conservation) or together with conventional agents. Of such approaches, locally applied protocols involving photo-antimicrobials suggest themselves, particularly as early intervention, e.g. in bacterial tonsillitis, would be curative without recourse to conventional drugs, and would thus prevent the development of more serious diseases such as pneumonia or meningitis. However, given the pharmaceutical industry's lack of investment in such approaches, support would be required from other areas of bioscience, such as the biomed or biotech sectors.

Peroxiredoxin-2 gene in Antheraea pernyi modulates immune functions and protect DNA damage.

Peroxiredoxins have been shown to protect insects from oxidative damage and to play a role in the immune system. In the present study, we cloned and characterized the Antheraea pernyi peroxiredoxin 2 (ApPrx-2) gene, then assessed its functional roles. The ApPrx-2 gene has a 687 bp open reading frame that encodes a protein with 288 amino acid residues. Quantitative real-time PCR analysis revealed that the mRNA levels of ApPrx-2 were highest in the hemocytes. Immune challenge assay revealed that ApPrx-2 transcription could be induced after microbial challenge. A DNA cleavage assay employing recombinant ApPrx-2 protein and a metal-catalyzed oxidation system showed that rApPrx-2 protein could protect supercoiled DNA against oxidative stress. The protein antioxidant activity of rApPrx-2 was examined, and it was found that rApPrx-2 exhibited a high level of antioxidant activity by removing H2O2. In addition, ApPrx-2 knockdown larvae had higher H2O2 levels and a lower survival rate when compared to controls. Interestingly, the antibacterial activity was significantly higher in ApPrx-2 depleted larvae compared with control. Overall, our findings indicate that ApPrx-2 may be involved in a range of physiological functions of A. pernyi, as it protects supercoiled DNA from oxidative stress and regulates antibacterial activity.

Potential of Flavonoids as Promising Phytotherapeutic Agents to Combat Multidrug-Resistant Infections.

BACKGROUND: Considering the limited number of current effective treatments, Multidrug- Resistant (MDR) illnesses have grown to be a serious concern to public health. It has become necessary to look for new antimicrobial drugs because of the emergence of resistance to numerous kinds of antibiotics. The use of flavonoids is one phytotherapeutic strategy that has been researched as a potential remedy for this issue. Secondary plant compounds called flavonoids have been found to have an antibacterial effect against resistant microorganisms. OBJECTIVE: This review seeks to give readers a glimpse into contemporary studies on flavonoids' potential to fight MDR infections. METHODS: A systematic search was conducted on electronic databases (PubMed, Scopus, and Google Scholar) using relevant keywords such as flavonoids, MDR infections, antimicrobial activity, and resistance microbes. Studies that investigated the antimicrobial activity of flavonoids against resistant microbes were included in this review. RESULTS: Most research found that flavonoids have antibacterial efficacy against resistant microorganisms, and some also showed that they have synergistic benefits with traditional antibiotics. The flavonoids quercetin, kaempferol, apigenin, and luteolin were the most often investigated ones. According to research, flavonoids affect microbial gene expression, inhibit microbial enzymes, and disrupt the integrity of microbial cell membranes. Additionally, a few studies have noted the flavonoids' low toxicity and safety. CONCLUSION: For the treatment of infections that are resistant to many drugs, flavonoids constitute a promising class of phytotherapeutic agents. To develop flavonoid-based treatment methods for treating MDR illnesses and assess the potential of flavonoids as adjuvants to conventional antimicrobial drugs, more study is required.

Genome sequence analysis of Malayan pangolin (Manis javanica) forensic samples reveals the presence of Paraburkholderia fungorum sequences.

Background: The Malayan pangolin (Manis javanica) is a placental mammal and is listed as Critically Endangered on the IUCN Red List of Threatened Species. Most previous attempts to breed pangolins in captivity have met with little success because of dietary issues, infections, and other complications, although a previous study reported breeding pangolins in captivity to the third generation. In our previous pangolin genome sequencing data analysis, we obtained a considerable amount of bacterial DNA from a pregnant female Malayan pangolin (named "UM3"), which was likely infected by Paraburkholderia fungorum-an agent of biodegradation and bioremediation in agriculture. Methodology: Here, we further confirmed and characterized this bacterial species using PCR, histological staining, whole-genome sequencing, and bioinformatics approaches. PCR assays with in-house designed primer sets and 16S universal primers showed clear positive bands in the cerebrum, cerebellum, lung, and blood of UM3 suggesting that UM3 might have developed septicaemia. Histological staining showed the presence of Gram-negative rod-shaped bacteria in the pangolin brain and lungs, indicating the colonization of the bacteria in these two organs. In addition, PCR screening of UM3's fetal tissues revealed the presence of P. fungorum in the gastrocnemius muscle, but not in other tissues that we examined. We also sequenced and reconstructed the genome of pangolin P. fungorum, which has a genome size of 7.7 Mbps. Conclusion: Our study is the first to present detailed evidence of the presence of P. fungorum in a pangolin and her fetus (although preliminary results were presented in our previous article). Here, we raise the concern that P. fungorum may potentially infect humans, especially YOPI (young, old, pregnant, and immunocompromised) people. Therefore, caution should be exercised when using this bacterial species as biodegradation or bioremediation agents in agriculture.

Caenorhabditis elegans LIN-24, a homolog of bacterial pore-forming toxin, protects the host from microbial infection.

Aerolysin-like pore-forming protein (af-PFP) superfamily members are double-edge swords that assist the bacterial infection but shied bacteria from the host by various mechanisms in some species including the toad Bombina maxima and zebrafish. While members of this family are widely expressed in all kingdoms, especially non-bacteria species, it remains unclear whether their anti-bacterial function is conserved. LIN-24 is an af-PFP that is constitutively expressed throughout the Caenorhabditis elegans lifespan. Here, we observed that LIN-24 knockdown reduced the maximum lifespan of worms. RNA-seq analysis identified 323 differentially expressed genes (DEGs) post-LIN-24 knockdown that were enriched in "immune response" and "lysosome pathway," suggesting a possible role for LIN-24 in resisting microbial infection. In line with this, we found that Pseudomonas aeruginosa 14 (PA14) infection induced LIN-24 expression, and that survival after PA14 infection was significantly reduced by LIN-24 knockdown. In contrast, LIN-24 overexpression (LIN-24-OE) conferred protection against PA14 infection, with worms showing longer survival time and reduced bacterial load. Weighted gene co-expression network analysis of LIN-24-OE worms showed that the highest correlation module was enriched in factors related to immunity and the defense response. Finally, by predicting transcription factors from RNA-seq data and knocking down candidate transcription factors in LIN-24-OE worms, we revealed that LIN-24 may protect worms against bacterial infection by stimulating DAF-16-mediated immune responses. These findings agree with our previous studies showing an anti-microbial role for the amphibian-derived af-PFP complex ßγ-CAT, suggesting that af-PFPs may play a conserved role in combatting microbial infections. Further research is needed to determine the roles this protein family plays in other physio-pathological processes, such as metabolism, longevity, and aging.

The impact of concurrent bacterial lung infection on immunotherapy in patients with non-small cell lung cancer: a retrospective cohort study.

Objective: To find out how bacterial lung infections (BLI) affect the effectiveness of therapy and the rate of pneumonia caused by pneumonia related to checkpoint inhibitors (CIP) in patients with non-small cell lung cancer (NSCLC) who are getting immunotherapy with checkpoint inhibitors (ICIs). Patients and methods: 507 NSCLC patients who received at least two ICI treatments between June 2020 and December 2022 at the Affiliated Hospital of Kunming University of Science and Technology(AHKUST) were included in a retrospective cohort study. Based on whether there was a concurrent BLI diagnosis from high-resolution CT scans of the chest, the patients were divided into two groups: 238 in the NSCLC with BLI group (NSCLC-BLI group), and 269 in the NSCLC alone group. The collected therapeutic outcome measures included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence rate of CIP. We analyzed the effect of BLI on the therapeutic efficacy of ICI treatment and the incidence rate of CIP in NSCLC patients.Inclusion criteria based on NSCLC patients staged I to IV according to the 8th edition of the International Association for Lung Cancer Research (IASLC). Results: The NSCLC-BLI group showed superior ORR to the NSCLC group when treated with ICIs. Multifactorial logistic regression and Cox analyses, adjusted for confounders, identified BLI as an independent positive prognostic factor for ORR (HR=0.482, 95%CI: 0.391-0.550; P<0.001) and PFS (HR=0.619; 95%CI: 0.551-0.771; P<0.001). No correlation between BLI and OS was found. Out of 26 cases of CIP, 12 were in the NSCLC-BLI group and 14 in the NSCLC group, with no significant difference in incidence (P=0.145). Conclusion: NSCLC patients with BLI receiving ICI treatment show superior ORR and PFS compared to NSCLC alone without an increased CIP risk, positioning BLI as a predictive factor for improved outcomes in NSCLC patients receiving ICIs. However, the study has limitations including its retrospective nature and lacking data on BLI bacteria types and levels, which could influence therapy outcomes.

A review of latrine front-end characteristics associated with microbial infection risk; reveals a lack of pathogen density data.

Unsafe sanitation accounts for an estimated 898,000 global deaths annually. The faecal pathogen transmission pathway is complex with several possible routes. Latrine front-end characteristics and usage behaviours are one key transmission pathway for microbial pathogens, however, there has not yet been a synthesis of the available research. This review aims to compare the microbial infection risks with latrine front-end components including any quantified microbial densities within the household latrines. This review was conducted with no restriction on the geographical location of the research. Of 118 studies reviewed, only ten (8%) have quantified the microbial density inside the household latrines compared to 109 (92%) measuring the infection risks. The reported risks were most frequent for specific bacterial (n = 34), and helminths infections (n = 32) compared to diarrhoea (n = 23), combined (n = 15), protozoan (n = 4), and viral (n = 4) infections. The infections risk decreased for using latrines lying at a higher position on the sanitation ladder (for example flush latrines) compared to those lying lower (for example pit latrines). The trend was similar for using floor materials that were easier to clean and less favourable for pathogen survival inside the latrines (for example, concrete as opposed to earth). Faecal coliforms were reported highest on the surface of the squat pan (743 CFU/cm2) of pour-flush latrines and helminths on earth floors of pit latrines (1.5 eggs and larvae per gram of soil). Irrespective of latrine type and its position on the sanitation ladder, a dirty latrine, evidenced by a visible lack of cleanliness, significantly increased the risk for all infections. This study recommends that effective microbial infection risk reduction in latrines can be gained efficiently by ensuring washable surfaces and consistent cleaning practices. Future studies should include more rigorous measurements of microbial densities in various latrine types incorporating the different front-end components and usage behaviours.

Evaluation of antimicrobial effect of olive leaves powder and its role in improving the broiler productivity, carcass traits, blood metabolites, and caecal microbiota.

The present study aims to evaluate the antimicrobial activity (in vitro study) of olive leaves powder (OLP) and its role in improving the broiler productivity, carcass criteria, blood indices, and antioxidant activity. A total of 270 one-day-old broiler chickens were distributed into 6 treatment groups as follows: the first group: basal diet without any supplementation, while the second, third, fourth, fifth, and sixth groups: basal diet supplemented with 50, 75, 100, 125, and 150 (µg/g), respectively. The in vitro study showed that the OLP has good antibacterial activity in the concentration-dependent matter; OLP 175 µg/mL inhibited the tested bacteria in the zones range of (0.8-4 cm), Klebsiella Pneumonaie (KP) was the most resistant bacteria to OLP concentration. The antioxidant activity of OLP increased with increasing the concentration of OLP compared to ascorbic acid, where OLP 175 µg/mL scavenged 91% of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radicals compared to 93% scavenging activity of ascorbic acid. Broiler chickens fed diets with OLP had significantly (P < 0.05) higher body weight (BW) and body weight growth (BWG) than the control birds. The treatment with OLP significantly reduced the feed intake (FI) and feed conversion rate (FCR) when compared to control. Groups supplemented with OLP showed decreased abdominal fat deposition and a significant increase in the net carcass and breast muscle weight. OLP improved birds' blood parameters in comparison with control birds. All pathogenic bacterial numbers in caecal samples were decreased with elevating OLP levels, but the cecal Lactobacillus bacterial count was increased. In conclusion, OLP supplementation improved broiler chickens' performance, carcass traits, and blood parameters. Moreover, OLP improved birds' liver functions (reduced Alanine transaminase [ALT] and aspartate aminotransferase [AST] levels) in comparison with control. In addition, OLP promoted the antioxidant status, minimized the harmful microbial load, and increased beneficial bacterial count in the cecal contents of broilers.

Repurposing Antimicrobial Protegrin-1 as a Dual-Function Amyloid Inhibitor via Cross-seeding.

Amyloids and antimicrobial peptides have traditionally been recognized as distinct families with separate biological functions and targets. However, certain amyloids and antimicrobial peptides share structural and functional characteristics that contribute to the development of neurodegenerative diseases. Specifically, the aggregation of amyloid-ß (Aß) and microbial infections are interconnected pathological factors in Alzheimer's disease (AD). In this study, we propose and demonstrate a novel repurposing strategy for an antimicrobial peptide of protegrin-1 (PG-1), which exhibits the ability to simultaneously prevent Aß aggregation and microbial infection both in vitro and in vivo. Through a comprehensive analysis using protein, cell, and worm assays, we uncover multiple functions of PG-1 against Aß, including the following: (i) complete inhibition of Aß aggregation at a low molar ratio of PG-1/Aß = 0.25:1, (ii) disassembly of the preformed Aß fibrils into amorphous aggregates, (iii) reduction of Aß-induced cytotoxicity in SH-SY5Y cells and transgenic GMC101 nematodes, and (iv) preservation of original antimicrobial activity against P.A., E.coli., S.A., and S.E. strains in the presence of Aß. Mechanistically, the dual anti-amyloid and anti-bacterial functions of PG-1 primarily arise from its strong binding to distinct Aß seeds (KD = 1.24-1.90 µM) through conformationally similar ß-sheet associations. This work introduces a promising strategy to repurpose antimicrobial peptides as amyloid inhibitors, effectively targeting multiple pathological pathways in AD.