Designing a multiepitope vaccine against the foodborne pathogenic bacteria Listeria monocytogenes using subtractive immunoinformatics approaches

Background: Listeria monocytogenes, a Gram-positive bacterium, is a prominent foodborne pathogen that causes listeriosis and poses substantial health hazards worldwide. The continuing risk of listeriosis outbreaks underlies the importance of designing an effective prevention strategy and developing a robust immune response by reverse vaccinology approaches. This study aimed to provide a critical approach for developing a potent multiepitope vaccine against this foodborne disease. Methods: A chimeric peptide construct containing 5 B-cell epitopes, 16 major histocompatibility complex I (MHC-I) epitopes, and 18 MHC-II epitopes were used to create a subunit vaccination against L. monocytogenes. The vaccine safety was evaluated by several online methods, and molecular docking was performed using ClusPro to determine the binding affinity. Immune simulation was performed using the C-ImmSimm server to demonstrate the immune response. Results: The results validated the antigenicity, non-allergenicity, and nontoxicity of the chimeric peptide construct, confirming its suitability as a subunit vaccine. Molecular docking showed a good score of 1276.5 and molecular dynamics simulations confirmed the construct’s efficacy, demonstrating its promise as a good candidate for listeriosis prophylaxis. The population coverage was as high as 91.04% with a good immune response, indicating good antigen presentation with dendritic cells and production of memory cells. Conclusions: The findings of this study highlight the potential of the designed chimeric peptide construct as an effective subunit vaccine against Listeria, paving the way for future advances in preventive methods and vaccine design.info:eu-repo/semantics/publishedVersio

Whole genome analysis of Tibetan Kefir-derived Lactiplantibacillus plantarum 12-3 elucidates its genomic architecture, antimicrobial and drug resistance, potential probiotic functionality and safety

Background: Lactiplantibacillus plantarum 12-3 holds great promise as a probiotic bacterial strain, yet its full potential remains untapped. This study aimed to better understand this potential therapeutic strain by exploring its genomic landscape, genetic diversity, CRISPR-Cas mechanism, genotype, and mechanistic perspectives for probiotic functionality and safety applications. Methods: L. plantarum 12-3 was isolated from Tibetan kefir grains and, subsequently, Illumina and Single Molecule Real-Time (SMRT) technologies were used to extract and sequence genomic DNA from this organism. After performing pan-genomic and phylogenetic analysis, Average Nucleotide Identity (ANI) was used to confirm the taxonomic identity of the strain. Antibiotic resistance gene analysis was conducted using the Comprehensive Antibiotic Resistance Database (CARD). Antimicrobial susceptibility testing, and virulence gene identification were also included in our genomic analysis to evaluate food safety. Prophage, genomic islands, insertion sequences, and CRISPR-Cas sequence analyses were also carried out to gain insight into genetic components and defensive mechanisms within the bacterial genome. Results: The 3.4 Mb genome of L. plantarum 12-3, was assembled with 99.1% completeness and low contamination. A total of 3234 genes with normal length and intergenic spacing were found using gene prediction tools. Pan-genomic studies demonstrated gene diversity and provided functional annotation, whereas phylogenetic analysis verified taxonomic identity. Our food safety study revealed a profile of antibiotic resistance that is favorable for use as a probiotic. Analysis of insertional sequences, genomic islands, and prophage within the genome provided information regarding genetic components and their possible effects on evolution. Conclusions: Pivotal genetic elements uncovered in this study play a crucial role in bacterial defense mechanisms and offer intriguing prospects for future genome engineering efforts. Moreover, our findings suggest further in vitro and in vivo studies are warranted to validate the functional attributes and probiotic potential of L. plantarum 12-3. Expanding the scope of the research to encompass a broader range of L. plantarum 12-3 strains and comparative analyses with other probiotic species would enhance our understanding of this organism's genetic diversity and functional properties.info:eu-repo/semantics/publishedVersio

Comparative genomics of food-derived probiotic Lactiplantibacillus plantarum K25 reveals its hidden potential, compactness, and efficiency

This study aimed to investigate the intricate genetic makeup of the Lactiplantibacillus plantarum K25 strain by conducting a comprehensive analysis of comparative genomics. The results of our study demonstrate that the genome exhibits a high-level efficiency and compactness, comprising a total of 3,199 genes that encode proteins and a GC content of 43.38%. The present study elucidates the evolutionary lineage of Lactiplantibacillus plantarum strains through an analysis of the degree of gene order conservation and synteny across a range of strains, thereby underscoring their closely interrelated evolutionary trajectories. The identification of various genetic components in the K25 strain, such as bacteriocin gene clusters and prophage regions, highlights its potential utility in diverse domains, such as biotechnology and medicine. The distinctive genetic elements possess the potential to unveil innovative therapeutic and biotechnological remedies in future. This study provides a comprehensive analysis of the L. plantarum K25 strain, revealing its remarkable genomic potential and presenting novel prospects for utilizing its unique genetic features in diverse scientific fields. The present study contributes to the existing literature on Lactiplantibacillus plantarum and sets the stage for prospective investigations and practical implementations that leverage the exceptional genetic characteristics of this adap organism

Assessing the probiotic potential, antioxidant, and antibacterial activities of oat and soy milk fermented with Lactiplantibacillus plantarum strains isolated from Tibetan Kefir

Sufficient intake of probiotics has been shown to help in the digestion, protect the body against pathogenic microorganisms and boost the immune system. Recently, due to high prevalence of milk allergies and lactose intolerance in population, the non-dairy based probiotic alternative are becoming increasing popular. In this context, the oat milk and soya milk-based fermented products can be an ideal alternative for the development of Lactic acid bacteria bacteria based probiotics. These bacteria can not only improve the product’s flavor and bioavailability but also increases its antibacterial and antioxidant capabilities due to fermentation process. The purpose of the resent work was to assess the antioxidant and probiotic properties of oat and soy milk that had been fermented with three different strains of Lactiplantibacillus plantarum (L. plantarum) including L. plantarum 12–3, L. plantarum K25, and L. plantarum YW11 isolated from Tibetan Kefir. Different validated assays were used to evaluate the probiotic properties, adhesion and survival in the digestive system (stomach, acid and bile salts resistance), antioxidant and antimicrobial activities and safety (ABTS and DPPH scavenging assays) of these strains. Results of the study showed that soya milk and oat milk fermented with L. plantarum strains possess promising probiotic, antibacterial and antioxidant properties. These results can be helpful to produce dairy-free probiotic replacements, which are beneficial for those who are unable to consume dairy products due to dietary or allergic restrictions

Molecular docking and density functional theory (DFT) studies on the conversion of linoleic acid into fatty acid metabolites by Lactiplantibacillus plantarum 12-3

The aim of this study was to evaluate the competency of Lactiplantibacillus plantarum 12-3 isolated from Tibetan kefir grains that how it converts linoleic acid (LA) into fatty acid metabolites and what are the main reactions involved in it. Also, we scrutinize the enzymes involved in this study via density functional theory (DFT) and in silico approaches. The taxonomic identity was performed using average nucleotide identity (ANI) analysis and to investigate its genome properties using the rapid annotations using subsystems technology (RAST) annotation service. After eliminating plasmid sequences to focus on core genomic information, ANI analysis was performed using the JSpecies Web Server. The results verified L. plantarum 12-3’s categorization as a member of the L. plantarum species, demonstrating good conservation and taxonomic relatedness. Heatmapper was used to visualize the ANI data clustering and heatmap, allowing the discovery of closely related strains within L. plantarum. RAST annotation of the genome revealed functional subsystems as well as metabolic pathways, cellular activities, and virulence factors. Several routes of future research might be pursued to further investigate the possible applications and distinctive properties of the L. plantarum 12-3 strain. To begin, comparative genomics studies with other L. plantarum strains would provide a better knowledge of the strain’s distinctive genetic variants and evolutionary adaptations. This may give light on its applicability for a variety of industrial uses, including food fermentation and probiotics

Correction: Shabbir et al. Effect of Yeast-Fermented Citrus Pulp as a Protein Source on Nutrient Intake, Digestibility, Nitrogen Balance and In Situ Digestion Kinetics in Nili Ravi Buffalo Bulls. Animals 2021, 11, 1713

Awais Shabbir was mistakenly written as “Muhammad Awais” in the original publication [...

Integrated track of nano-informatics coupling with the enrichment concept in developing a novel nanoparticle targeting ERK protein in Naegleria fowleri

Naegleria fowleri is a free-living amoeba that causes primary amoebic meningoencephalitis. Despite combination drug therapies, N. fowleri is not sensitive to current drug therapies, contributing to the pathogen’s mortality rate of 98%. To enable rational drug designing, this study has proposed an integrated track of nanotechnology coupling with the enrichment concept. In the current study, zinc oxide nanoparticles (ZNP) were screened against ERK protein, which is responsible for the production of pro-inflammatory cytokines that cause brain disturbance in N. fowleri infection. Furthermore, an enrichment analysis has been executed to increase the efficiency of the ZNP through the addition of two amines and one chlorine group. The computational prediction of zeta potential, cytotoxicity, organ toxicity, calculations of binding free energy, and ADMET analysis shows that it is stable and possesses no toxic effect. Amine + chlorine enriched ZNP resulted in a binding energy of −7.8 kcal/mol, a zeta potential reliability of −40 mV, a cytotoxicity of −0.0002, inactive against all the targeted organ models, ADMET profiling shows a molecular weight of 320.54 g/mol, a lipophilicity of −0.99, high water solubility, and good gastrointestinal tract absorption. This proposed invention represents the future work for in vitro in combating this devastating disease toward a reliable therapeutic target with drugs that specifically aimed to inhibit the infection

Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib

BCR-ABL1 is a fusion protein as a result of a unique chromosomal translocation (producing the so-called Philadelphia chromosome) that serves as a clinical biomarker primarily for chronic myeloid leukemia (CML); the Philadelphia chromosome also occurs, albeit rather rarely, in other types of leukemia. This fusion protein has proven itself to be a promising therapeutic target. Exploiting the natural vitamin E molecule gamma-tocotrienol as a BCR-ABL1 inhibitor with deep learning artificial intelligence (AI) drug design, this study aims to overcome the present toxicity that embodies the currently provided medications for (Ph+) leukemia, especially asciminib. Gamma-tocotrienol was employed in an AI server for drug design to construct three effective de novo drug compounds for the BCR-ABL1 fusion protein. The AIGT’s (Artificial Intelligence Gamma-Tocotrienol) drug-likeliness analysis among the three led to its nomination as a target possibility. The toxicity assessment research comparing AIGT and asciminib demonstrates that AIGT, in addition to being more effective nonetheless, is also hepatoprotective. While almost all CML patients can achieve remission with tyrosine kinase inhibitors (such as asciminib), they are not cured in the strict sense. Hence it is important to develop new avenues to treat CML. We present in this study new formulations of AIGT. The docking of the AIGT with BCR-ABL1 exhibited a binding affinity of −7.486 kcal/mol, highlighting the AIGT’s feasibility as a pharmaceutical option. Since current medical care only exclusively cures a small number of patients of CML with utter toxicity as a pressing consequence, a new possibility to tackle adverse instances is therefore presented in this study by new formulations of natural compounds of vitamin E, gamma-tocotrienol, thoroughly designed by AI. Even though AI-designed AIGT is effective and adequately safe as computed, in vivo testing is mandatory for the verification of the in vitro results

Mix-match synthesis of nanosynbiotics from probiotics and prebiotics to counter gut dysbiosis via AI integrated formulation profiling

Abstract Antibiotics, improper food, and stress have created a dysbiotic state in the gut and almost 81% of the world’s population has been affected due to the pandemic of COVID-19 and the prevalence of dengue virus in the past few years. The main intent of this study is to synthesize nanosynbiotics as nu traceuticals by combining probiotics, and prebiotics with nanoformulation. The effectiveness of the nanosynbiotics was evaluated using a variety of Nutra-pharmacogenetic assays leading to an AI-integrated formulation profiling was assessed by using machine learning methods. Consequently, Acetobacter oryzoeni as a probiotic and inulin as a prebiotic has been chosen and iron-mediated nanoformulation of symbiotic is achieved. Nanosynbiotics possessed 89.4, 96.7, 93.57, 83.53, 88.53% potential powers of Nutra-pharmacogenetic assays. Artificial intelligent solid dispersion formulation of nanosynbiotics has high dissolution, absorption, distribution, and synergism, in addition, they are non-tox, non-allergen and have a docking score of − 10.83 kcal/mol, implying the best interaction with Pregnane X receptor involved in dysbiosis. The potential of nanosynbiotics to revolutionize treatment strategies through precise targeting and modulation of the gut microbiome for improved health outcomes and disease management is promising. Their transformational influence is projected to be powered by integration with modern technology and customized formulas. Further in-vivo studies are required for the validation of nanosynbiotics as nutraceuticals