Algae-Mediated Removal of Prevalent Genotoxic Antibiotics: Molecular Perspective on Algae-Bacteria Consortia and Bioreactor-Based Strategies.

Antibiotic pollution poses a potential risk of genotoxicity, as antibiotics released into the environment can induce DNA damage and mutagenesis in various organisms. This pollution, stemming from pharmaceutical manufacturing, agriculture, and improper disposal, can disrupt aquatic ecosystems and potentially impact human health through the consumption of contaminated water and food. The removal of genotoxic antibiotics using algae-mediated approaches has gained considerable attention due to its potential for mitigating the environmental and health risks associated with these compounds. The paper provides an in-depth examination of the molecular aspects concerning algae and bioreactor-driven methodologies utilized for the elimination of deleterious antibiotics. The molecular analysis encompasses diverse facets, encompassing the discernment and profiling of algae species proficient in antibiotic degradation, the explication of enzymatic degradation pathways, and the refinement of bioreactor configurations to augment removal efficacy. Emphasizing the significance of investigating algal approaches for mitigating antibiotic pollution, this paper underscores their potential as a sustainable solution, safeguarding both the environment and human health.

Nutritional Composition and Therapeutic Potential of Pineapple Peel - A Comprehensive Review.

Pineapple (Ananas comosus), the succulent and vibrant tropical fruit, is a symbol of exoticism and sweetness that captures the hearts and palates of people around the world. The pineapple peel, often considered as waste, has garnered attention for its potential applications. The pineapple peel is rich in essential nutrients, including calcium, potassium, vitamin C, carbohydrates, dietary fiber, and water, making it beneficial for the digestive system, weight management, and overall balanced nutrition. It contains significant amounts of sugars such as sucrose, glucose, and fructose, along with citric acid as the predominant organic acid. The peel also contains bromelain, a proteolytic enzyme known for its digestive properties. Studies have highlighted the pharmacological properties of pineapple peel, such as its potential anti-parasitic effects, alleviation of constipation, and benefits for individuals with irritable bowel syndrome (IBS). Efforts are being made to promote the utilization of pineapple peel as a valuable resource rather than mere waste. Its applications range from the production of vinegar, alcohol, and citric acid to the development of various food products, including squash, syrup, jelly, and pickles. Further research and innovation are required to fully explore the potential of pineapple peel and establish sustainable practices for its utilization, contributing to waste reduction and the development of value-added products.

Lipoplexes' Structure, Preparation, and Role in Managing Different Diseases.

Lipid-based vectors are becoming promising alternatives to traditional therapies over the last 2 decades specially for managing life-threatening diseases like cancer. Cationic lipids are the most prevalent non-viral vectors utilized in gene delivery. The increasing number of clinical trials about lipoplex-based gene therapy demonstrates their potential as well-established technology that can provide robust gene transfection. In this regard, this review will summarize this important point. These vectors however have a modest transfection efficiency. This limitation can be partly addressed by using functional lipids that provide a plethora of options for investigating nucleic acid-lipid interactions as well as in vitro and in vivo nucleic acid delivery for biomedical applications. Despite their lower gene transfer efficiency, lipid-based vectors such as lipoplexes have several advantages over viral ones: they are less toxic and immunogenic, can be targeted, and are simple to produce on a large scale. Researchers are actively investigating the parameters that are essential for an effective lipoplex delivery method. These include factors that influence the structure, stability, internalization, and transfection of the lipoplex. Thorough understanding of the design principles will enable synthesis of customized lipoplex formulations for life-saving therapy.

Microbial adaptation to different environmental conditions: molecular perspective of evolved genetic and cellular systems.

Microorganisms are ubiquitous on Earth and can inhabit almost every environment. In a complex heterogeneous environment or in face of ecological disturbance, the microbes adjust to fluctuating environmental conditions through a cascade of cellular and molecular systems. Their habitats differ from cold microcosms of Antarctica to the geothermal volcanic areas, terrestrial to marine, highly alkaline zones to the extremely acidic areas and freshwater to brackish water sources. The diverse ecological microbial niches are attributed to the versatile, adaptable nature under fluctuating temperature, nutrient availability and pH of the microorganisms. These organisms have developed a series of mechanisms to face the environmental changes and thereby keep their role in mediate important ecosystem functions. The underlying mechanisms of adaptable microbial nature are thoroughly investigated at the cellular, genetic and molecular levels. The adaptation is mediated by a spectrum of processes like natural selection, genetic recombination, horizontal gene transfer, DNA damage repair and pleiotropy-like events. This review paper provides the fundamentals insight into the microbial adaptability besides highlighting the molecular network of microbial adaptation under different environmental conditions.

Krüppel-like factors family regulation of adipogenic markers genes in bovine cattle adipogenesis.

Intramuscular fat (IMF) content is a crucial determinant of meat quality traits in livestock. A network of transcription factors act in concert to regulate adipocyte formation and differentiation, which in turn influences intramuscular fat. Several genes and associated transcription factors have been reported to influence lipogenesis and adipogenesis during fetal and subsequent growth stage. Specifically in cattle, Krüppel-like factors (KLFs), which represents a family of transcription factors, have been reported to be involved in adipogenic differentiation and development. KLFs are a relatively large group of zinc-finger transcription factors that have a variety of functions in addition to adipogenesis. In mammals, the participation of KLFs in cell development and differentiation is well known. Specifically in the context of adipogenesis, KLFs function either as positive (KLF4, KLF5, KLF6, KLF8, KLF9, KLF10, KLF11, KLF12, KLF13, KLF14 and KLF15) or negative organizers (KLF2, KLF3 and KLF7), by a variety of different mechanisms such as crosstalk with C/EBP and PPARγ. In this review, we aim to summarize the potential functions of KLFs in regulating adipogenesis and associated pathways in cattle. Furthermore, the function of known bovine adipogenic marker genes, and associated transcription factors that regulate the expression of these marker genes is also summarized. Overall, this review will provide an overview of marker genes known to influence bovine adipogenesis and regulation of expression of these genes, to provide insights into leveraging these genes and transcription factors to enhance breeding programs, especially in the context of IMF deposition and meat quality.

Prospects of advanced metagenomics and meta-omics in the investigation of phytomicrobiome to forecast beneficial and pathogenic response.

Microorganisms dwell in diverse plant niches as non-axenic biotic components that are beneficial as well pathogenic for the host. They improve nutrients-uptake, stress tolerance, phytohormone synthesis, and strengthening the defense system through phyllosphere, rhizosphere, and endosphere. The negative consequences of the microbial communities are largely in the form of diseases characterized by certain symptoms such as gall, cankers, rots etc. Uncultivable and unspecified nature of different phytomicrobiomes communities is a challenge in the management of plant disease, a leading cause for the loss of the plant products. Metagenomics has opened a new gateway for the exploration of microorganisms that are hitherto unknown, enables investigation of the functional aspect of microbial gene products through metatranscriptomics and metabolomics. Metagenomics offers advantages of characterizing previously unknown microorganisms from extreme environments like hot springs, glaciers, deep seas, animal gut etc. besides bioprospecting gene products such as Taq polymerase, bor encoded indolotryptoline, hydrolases, and polyketides. This review provides a detailed account of the phytomicrobiome networks and highlights the importance and limitations of metagenomics and other meta-omics approaches for the understanding of plant microbial diversity with special focus on the disease control and its management.

Insights into the beneficial roles of dark septate endophytes in plants under challenging environment: resilience to biotic and abiotic stresses.

Dark septate endophytes (DSE) exert a plethora of effects in regulating plant growth, signalling and stress tolerance. The advent of metagenomics has led to the identification of various species of DSE to be associated with plant organs. They are known to modulate growth, nutrient uptake, phytohormone biosynthesis and production of active bioconstituents in several plants. The interactions between the DSE and host plants are mostly mutualistic but they can also be neutral or exhibit negative interactions. The DSE has beneficial role in removal/sequestration of toxic heavy metals from various environmental sites. Here, we discuss the beneficial role of DSE in enhancing plant tolerance to heavy metal stress, drought conditions, high salinity and protection from various plant pathogens. Furthermore, the underlying mechanism of stress resilience facilitated by DSE-plant interaction has also been discussed. The article also provides insights to some important future perspectives associated with DSE-mediated phytoremediation and reclamation of polluted land worldwide thus facilitating sustainable agriculture.

Unraveling molecular signatures in rare bone tumors and navigating the cancer pathway landscapes for targeted therapeutics.

Rare cancers (RCs), which account for over 20% of cancer cases, face significant research and treatment challenges due to their limited prevalence. This results in suboptimal outcomes compared to more common malignancies. Rare bone tumors (RBTs) constitute 5-10% of rare cancer cases and pose unique diagnostic complexities. The therapeutic potential of anti-cancer drugs for RBTs remains largely unexplored. Identifying molecular alterations in cancer-related genes and their associated pathways is essential for precision medicine in RBTs. Small molecule inhibitors and monoclonal antibodies targeting specific RBT-associated proteins show promise. Ongoing clinical trials aim to define RBT biomarkers, subtypes, and optimal treatment contexts, including combination therapies and immunotherapeutic agents. This review addresses the challenges in diagnosing, treating, and studying RBTs, shedding light on the current state of RBT biomarkers, potential therapeutic targets, and promising inhibitors. Rare cancers demand attention and innovative solutions to improve clinical outcomes.

Characterization of thermostable carboxypeptidase from high-altitude hot spring metagenome.

This study explored the metagenome of the Pir Panjal Hot Spring (PPHS) to identify thermostable hydrolases. The carboxypeptidase (CarP) gene was successfully amplified and cloned into Escherichia coli DH5-α cells, followed by expression in E. coli BL21-DE3 cells. The CarP enzyme was comprehensively characterized in vitro. Sequencing analysis revealed an open reading frame encoding a functional protein of 504 amino acids, with a molecular weight of 58.65 kDa and an isoelectric point of 4.81. The CarP protein was purified using Ni-His affinity chromatography, and the experimental molecular weight matched in silico predictions. The enzyme exhibited significant thermostability and alkaliphilic properties, with optimal activity at 70 °C and pH 10.0. Additionally, the presence of Zn+2 ions at concentrations of 5 and 10 mmol/L enhanced protease activity by 1.4 and 1.5-fold, respectively. This study reports the discovery of a novel, multifunctional, and thermostable CarP from hot-spring metagenomes. The enzyme's stability against high temperatures, metal ions, surfactants, and inhibitors, along with its specific substrate interactions, highlights its potential for various biotechnological applications.

Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for Sarcoma Therapy.

Sarcoma is a heterogeneous group of malignancies often resistant to conventional chemotherapy and radiation therapy. The phosphatidylinositol-3-kinase/ protein kinase B /mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway has emerged as a critical cancer target due to its central role in regulating key cellular processes such as cell growth, proliferation, survival, and metabolism. Dysregulation of this pathway has been implicated in the development and progression of bone sarcomas (BS) and soft tissue sarcomas (STS). PI3K/Akt/mTOR inhibitors have shown promising preclinical and clinical activity in various cancers. These agents can inhibit the activation of PI3K, Akt, and mTOR, thereby reducing the downstream signaling events that promote tumor growth and survival. In addition, PI3K/Akt/mTOR inhibitors have been shown to enhance the efficacy of other anticancer therapies, such as chemotherapy and radiation therapy. The different types of PI3K/Akt/mTOR inhibitors vary in their specificity, potency, and side effect profiles and may be effective depending on the specific sarcoma type and stage. The molecular targeting of PI3K/Akt/mToR pathway using drugs, phytochemicals, nanomaterials (NMs), and microbe-derived molecules as Pan-PI3K inhibitors, selective PI3K inhibitors, and dual PI3K/mTOR inhibitors have been delineated. While there are still challenges to be addressed, the preclinical and clinical evidence suggests that these inhibitors may significantly improve patient outcomes. Further research is needed to understand the potential of these inhibitors as sarcoma therapeutics and to continue developing more selective and effective agents to meet the clinical needs of sarcoma patients.

Metagenomics in the fight against zoonotic viral infections: A focus on SARS-CoV-2 analogues.

Zoonotic viral infections continue to pose significant threats to global public health, as highlighted by the COVID-19 pandemic caused by the SARS-CoV-2 virus. The emergence of SARS-CoV-2 served as a stark reminder of the potential for zoonotic transmission of viruses from animals to humans. Understanding the origins and dynamics of zoonotic viruses is critical for early detection, prevention, and effective management of future outbreaks. Metagenomics has emerged as a powerful tool for investigating the virome of diverse ecosystems, shedding light on the diversity of viral populations, their hosts, and potential zoonotic spillover events. We provide an in-depth examination of metagenomic approaches, including, NGS metagenomics, shotgun metagenomics, viral metagenomics, and single-virus metagenomics, highlighting their strengths and limitations in identifying and characterizing zoonotic viral pathogens. This review underscores the pivotal role of metagenomics in enhancing our ability to detect, monitor, and mitigate zoonotic viral infections, using SARS-CoV-2 analogues as a case study. We emphasize the need for continued interdisciplinary collaboration among virologists, ecologists, and bioinformaticians to harness the full potential of metagenomic approaches in safeguarding public health against emerging zoonotic threats.

Environmental resilience through artificial intelligence: innovations in monitoring and management.

The rapid rise of artificial intelligence (AI) technology has revolutionized numerous fields, with its applications spanning finance, engineering, healthcare, and more. In recent years, AI's potential in addressing environmental concerns has garnered significant attention. This review paper provides a comprehensive exploration of the impact that AI has on addressing and mitigating critical environmental concerns. In the backdrop of AI's remarkable advancement across diverse disciplines, this study is dedicated to uncovering its transformative potential in the realm of environmental monitoring. The paper initiates by tracing the evolutionary trajectory of AI technologies and delving into the underlying design principles that have catalysed its rapid progression. Subsequently, it delves deeply into the nuanced realm of AI applications in the analysis of remote sensing imagery. This includes an intricate breakdown of challenges and solutions in per-pixel analysis, object detection, shape interpretation, texture evaluation, and semantic understanding. The crux of the review revolves around AI's pivotal role in environmental control, examining its specific implementations in wastewater treatment and solid waste management. Moreover, the study accentuates the significance of AI-driven early-warning systems, empowering proactive responses to environmental threats. Through a meticulous analysis, the review underscores AI's unparalleled capacity to enhance accuracy, adaptability, and real-time decision-making, effectively positioning it as a cornerstone in shaping a sustainable and resilient future for environmental monitoring and preservation.

Carbon nanotubes in plant dynamics: Unravelling multifaceted roles and phytotoxic implications.

Carbon nanotubes (CNTs) have emerged as a promising frontier in plant science owing to their unique physicochemical properties and versatile applications. CNTs enhance stress tolerance by improving water dynamics and nutrient uptake and activating defence mechanisms against abiotic and biotic stresses. They can be taken up by roots and translocated within the plant, impacting water retention, nutrient assimilation, and photosynthesis. CNTs have shown promise in modulating plant-microbe interactions, influencing symbiotic relationships and mitigating the detrimental effects of phytopathogens. CNTs have demonstrated the ability to modulate gene expression in plants, offering a powerful tool for targeted genetic modifications. The integration of CNTs as sensing elements in plants has opened new avenues for real-time monitoring of environmental conditions and early detection of stress-induced changes. In the realm of agrochemicals, CNTs have been explored for their potential as carriers for targeted delivery of nutrients, pesticides, and other bioactive compounds. CNTs have the potential to demonstrate phytotoxic effects, detrimentally influencing both the growth and developmental processes of plants. Phytotoxicity is characterized by induction of oxidative stress, impairment of cellular integrity, disruption of photosynthetic processes, perturbation of nutrient homeostasis, and alterations in gene expression. This review aims to provide a comprehensive overview of the current state of knowledge regarding the multifaceted roles of CNTs in plant physiology, emphasizing their potential applications and addressing the existing challenges in translating this knowledge into sustainable agricultural practices.

Microbial exopolysaccharides: Unveiling the pharmacological aspects for therapeutic advancements.

Microbial exopolysaccharides (EPSs) have emerged as a fascinating area of research in the field of pharmacology due to their diverse and potent biological activities. This review paper aims to provide a comprehensive overview of the pharmacological properties exhibited by EPSs, shedding light on their potential applications in various therapeutic areas. The review begins by introducing EPSs, exploring their various sources, significance in microbial growth and survival, and their applications across different industries. Subsequently, a thorough examination of the pharmaceutical properties of microbial EPSs unveils their antioxidant, immunomodulatory, antimicrobial, antidepressant, antidiabetic, antiviral, antihyperlipidemic, hepatoprotective, anti-inflammatory, and anticancer activities. Mechanistic insights into how different EPSs exert these therapeutic effects have also been discussed in this review. The review also provides comprehensive information about the monosaccharide composition, backbone, branches, glycosidic bonds, and molecular weight of pharmacologically active EPSs from various microbial sources. Furthermore, the factors that can affect the pharmacological activities of EPSs and approaches to improve the EPSs' pharmacological activity have also been discussed. In conclusion, this review illuminates the immense pharmaceutical promise of microbial EPS as versatile bioactive compounds with wide-ranging therapeutic applications. By elucidating their structural features, biological activities, and potential applications, this review aims to catalyze further research and development efforts in leveraging the pharmaceutical potential of microbial EPS for the advancement of human health and well-being, while also contributing to sustainable and environmentally friendly practices in the pharmaceutical industry.

Fighting Carcinogenesis with Plant Metabolites by Weakening Proliferative Signaling and Disabling Replicative Immortality Networks of Rapidly Dividing and Invading Cancerous Cells.

BACKGROUND: Cancer, an uncontrolled multistage disease causing swift division of cells, is a leading disease with the highest mortality rate. Cellular heterogeneity, evading growth suppressors, resisting cell death, and replicative immortality drive the tumor progression by resisting the therapeutic action of existing anticancer drugs through a series of intrinsic and extrinsic cellular interactions. The innate cellular mechanisms also regulate the replication process as a fence against proliferative signaling, enabling replicative immortality through telomere dysfunction. AREA COVERED: The conventional genotoxic drugs have several off-target and collateral side effects associated with them. Thus, the need for the therapies targeting cyclin-dependent kinases or P13K signaling pathway to expose cancer cells to immune destruction, deactivation of invasion and metastasis, and maintaining cellular energetics is imperative. Compounds with anticancer attributes isolated from plants and rich in alkaloids, terpenes, and polyphenols have proven to be less toxic and highly targetspecific, making them biologically significant. This has opened a gateway for the exploration of more novel plant molecules by signifying their role as anticancer agents in synergy and alone, making them more effective than the existing cytotoxic regimens. EXPERT OPINION: In this context, the current review presented recent data on cancer cases around the globe, along with discussing the fundamentals of proliferative signaling and replicative immortality of cancer cells. Recent findings were also highlighted, including antiproliferative and antireplicative action of plant-derived compounds, besides explaining the need for improving drug delivery systems.

Discovering Deleterious Single Nucleotide Polymorphisms of Human AKT1 Oncogene: An In Silico Study.

BACKGROUND: AKT1 is a serine/threonine kinase necessary for the mediation of apoptosis, angiogenesis, metabolism, and cell proliferation in both normal and cancerous cells. The mutations in the AKT1 gene have been associated with different types of cancer. Further, the AKT1 gene mutations are also reported to be associated with other diseases such as Proteus syndrome and Cowden syndromes. Hence, this study aims to identify the deleterious AKT1 missense SNPs and predict their effect on the function and structure of the AKT1 protein using various computational tools. METHODS: Extensive in silico approaches were applied to identify deleterious SNPs of the human AKT1 gene and assessment of their impact on the function and structure of the AKT1 protein. The association of these highly deleterious missense SNPs with different forms of cancers was also analyzed. The in silico approach can help in reducing the cost and time required to identify SNPs associated with diseases. RESULTS: In this study, 12 highly deleterious SNPs were identified which could affect the structure and function of the AKT1 protein. Out of the 12, four SNPs-namely, G157R, G159V, G336D, and H265Y-were predicted to be located at highly conserved residues. G157R could affect the ligand binding to the AKT1 protein. Another highly deleterious SNP, R273Q, was predicted to be associated with liver cancer. CONCLUSIONS: This study can be useful for pharmacogenomics, molecular diagnosis of diseases, and developing inhibitors of the AKT1 oncogene.

Forty years of research and development on forensic genetics: A bibliometric analysis.

The current study aims to investigate the research publication trends in the field of forensic genetics using Bibliometric analysis. An extensive search of the Scopus database was conducted to identify scholarly articles on forensic genetics published between 1977 and 2022, and a data set comprising 2945 articles was obtained. The analysis was carried out using VOSviewer, RStudio, MS Excel and MS Access to investigate the annual publication trend, most productive journals, organizations/authors/countries, authorship and citation patterns, most cited documents/articles and co-occurrence of keywords. The results revealed the first article in the field of forensic genetics was published in 1977. By the end of 1999, only 15 articles were published. Since then, there has been a considerable increase in the yearly number of publications and post-2006, there were more than 100 yearly published articles. USA, China, Spain, Germany and United Kingdom were found to be the most productive countries. Among various organizations, the Institute of Legal Medicine, Innsbruck Medical University, Austria was found to be the most productive organization. In terms of the number of publications and citations, Morling N. was found to be the most prolific author. The highest number of articles were published in Forensic Science International: Genetics, contributing about 34% of the total articles published in different sources/journals. The document with the highest number of citations was "HOMER N, 2008, PLOS GENET", with a total of 750 citations. The most frequent keywords were forensic genetics and forensic science, followed by STR, population genetics, DNA, mt-DNA and DNA-typing. The results also revealed that there had been collaborative research among countries, organizations and authors, which helps in the exchange of ideas across disciplines, developing new skills, getting access to financial resources and generating quality results.

Building the taxonomic profile of the Riniaie Marwah hot spring of Kishtwar in Jammu and Kashmir: the first high-throughput sequencing-based metagenome study.

Background and Objectives: Rinaie Marwah hot spring Kishtwar (RMHSK) is one of the geothermal springs located at 33°51'51″N 75°32'07″E with an elevation of 2134 meters above sea level in Jammu and Kashmir, India. We aimed to study the microbial diversity of this geothermal spring using metagenomics. Materials and Methods: In the present study, physiochemical parameters including temperature (65-75°C), pH (6. 9-8. 8), hardness (250 ppm), and mineral content was measured along with the microbial diversity using Illumina MiSeq metagenome-based 16s amplicon sequencing (V3-V4). The sequence reads were classified taxonomically into 31 phyla, 71 classes, 152 orders, 256 families, 410 genus, and 665 species. QIIME 2 (Quantitative Insights into Microbial Ecology), an extensible, powerful, and decentralized analytical tool, was used for taxonomic analysis. Results: Bacteroidota (32. 57%) was the dominant phylum, Bacteroidia (32. 51%) the dominant class, Bacteroidales (16. 6%) the dominant order, and Lentimicrobiaceae (14. 23%) was the dominant family per the abundance analysis. Shannon (2. 28) and Chao 1 (87. 0) diversity indices support the existence of higher microbial diversity in RMHSK (50717 OTUs). Conclusion: The microbial diversity of RMHSK is reported for the first time through a metagenomic study. Identification of microorganisms with characteristics that are relevant to industries.

Genome centric engineering using ZFNs, TALENs and CRISPR-Cas9 systems for trait improvement and disease control in Animals.

Livestock is an essential life commodity in modern agriculture involving breeding and maintenance. The farming practices have evolved mainly over the last century for commercial outputs, animal welfare, environment friendliness, and public health. Modifying genetic makeup of livestock has been proposed as an effective tool to create farmed animals with characteristics meeting modern farming system goals. The first technique used to produce transgenic farmed animals resulted in random transgene insertion and a low gene transfection rate. Therefore, genome manipulation technologies have been developed to enable efficient gene targeting with a higher accuracy and gene stability. Genome editing (GE) with engineered nucleases-Zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) regulates the targeted genetic alterations to facilitate multiple genomic modifications through protein-DNA binding. The application of genome editors indicates usefulness in reproduction, animal models, transgenic animals, and cell lines. Recently, CRISPR/Cas system, an RNA-dependent genome editing tool (GET), is considered one of the most advanced and precise GE techniques for on-target modifications in the mammalian genome by mediating knock-in (KI) and knock-out (KO) of several genes. Lately, CRISPR/Cas9 tool has become the method of choice for genome alterations in livestock species due to its efficiency and specificity. The aim of this review is to discuss the evolution of engineered nucleases and GETs as a powerful tool for genome manipulation with special emphasis on its applications in improving economic traits and conferring resistance to infectious diseases of animals used for food production, by highlighting the recent trends for maintaining sustainable livestock production.

Secreted Aspartyl Proteinases Targeted Multi-Epitope Vaccine Design for Candida dubliniensis Using Immunoinformatics.

Candida dubliniensis is an opportunistic pathogen associated with oral and invasive fungal infections in immune-compromised individuals. Furthermore, the emergence of C. dubliniensis antifungal drug resistance could exacerbate its treatment. Hence, in this study a multi-epitope vaccine candidate has been designed using an immunoinformatics approach by targeting C. dubliniensis secreted aspartyl proteinases (SAP) proteins. In silico tools have been utilized to predict epitopes and determine their allergic potential, antigenic potential, toxicity, and potential to elicit interleukin-2 (IL2), interleukin-4 (IL4), and IFN-γ. Using the computational tools, eight epitopes have been predicted that were then linked with adjuvants for final vaccine candidate development. Computational immune simulation has depicted that the immunogen designed emerges as a strong immunogenic candidate for a vaccine. Further, molecular docking and molecular dynamics simulation analyses revealed stable interactions between the vaccine candidate and the human toll-like receptor 5 (TLR5). Finally, immune simulations corroborated the promising candidature of the designed vaccine, thus calling for further in vivo investigation.