Intrinsic physiochemical insights to green synthesized Ag-decorated GO nanosheet for photoluminescence and in vivo cellular biocompatibility with embryonic zebrafish.

The advancement of nanotechnology and their application has intrigued a significant interest in green synthesis and application of organic and inorganic nanomaterials like graphene oxide (GO) and silver nanoparticles (AgNP). This study explores the intrinsic physiochemical properties of silver (Ag)-decorated graphene oxide (GO) nanosheets synthesized via a green approach, focusing on their photoluminescence behaviour and in vivo cellular biocompatibility with embryonic zebrafish. The nanocomposites were characterized using various spectroscopic and microscopic techniques to elucidate their structural and optical properties. Results reveal that the Ag-decorated GO nanosheets exhibit enhanced photoluminescence compared to pristine GO with an SPR at 405 nm and emission at 676 nm, attributed to the synergistic effects of Ag nanoparticles and GO. In addition, in vivo biocompatibility assessments using embryonic zebrafish demonstrate minimal cytotoxicity and high cellular viability upon exposure to the nanocomposites with an LC50 of 38 µg/ml, indicating their potential for biomedical applications. Further investigations into the interactions between the nanomaterials and biological systems provide valuable insights into their safety profile and suggest their suitability for various biomedical and therapeutic applications. Overall, this study offers a comprehensive understanding of the physiochemical characteristics and biological compatibility of Ag-decorated GO nanosheets, contributing to the advancement of nanotechnology in biomedicine and related fields.

Controlled in vivo intrinsic detrimental effect of d-Limonene channelized by influential proximal interaction through apoptosis and steatosis in embryonic zebrafish (Danio rerio).

Bioaccumulation of d-Limonene in environment due to the aggrandised usage of their natural sources like citrus food wastes and industrial day to day life products has raised concern to their biotoxicity to environment biotic health. Moreover, their after-usage discharge to aquatic system has enhanced the distress of posing threat and needs attention. This study entails mechanistic and molecular evaluation of in-vivo biotoxicity of d-Limonene in zebrafish embryo models. Experimental analysis excavated the controlled concentration-dependent morphological, physiological and cellular in-vivo impact of d-Limonene in zebrafish embryos through significant changes in oxidative stress, steatosis and apoptosis regulated via 6-fold and 5-fold mRNA expression change in p53 and Sod1 genes. Computational evaluation deduced the cellular mechanism of d-limonene biotoxicity as irregularities in oxidative stress, apoptosis and steatosis due of their intrinsic interaction with metabolic proteins like Zhe1a (-4.8 Kcal/mol), Sod1(-5.3 Kcal/mol), p53, caspase3 and apoa1 leading to influential change in structural and functional integrity of the metabolic proteins. The study unravelled the measured in-vivo biotoxicity of d-Limonene at cellular and molecular level to advocate the controlled usage of d-Limonene related natural and industrial product for a sustainable environmental health.

Detrimental consequences of micropolymers associated plasticizers on endocrinal disruption.

The prevalence of polymer usage in everyday activities has emerged as a detriment to both human life and the environment. A large number of studies describe severe impacts of micropolymers (MP) and nanopolymers (NP) on various organ systems, including the endocrine system. Additionally, plasticizers utilized as additives have been identified as endocrine-disrupting chemicals (EDCs). MP/NP, along with associated plasticizers, affect principal signalling pathways of endocrine glands such as the pituitary, thyroid, adrenal, and gonads, thereby disrupting hormone function and metabolic processes crucial for maintaining homeostasis, fertility, neural development, and fetal growth. This review delves into the sources, distribution, and effects of micropolymers, nanopolymers, and associated plasticizers acting as EDCs. Furthermore, it provides a detailed review of the mechanisms underlying endocrine disruption in relation to different types of MP/NP.

Molecular insights to in vitro biocompatibility of endodontic Pulpotec with macrophages determined by oxidative stress and apoptosis.

Pulp therapy has been emerged as a one of the efficient therapies in the field of endodontics. Among different types of new endodontic materials, pulpotec has been materialized as a recognized material for vital pulp therapy. However, its efficacy has been challenged due to lack of information about its cellular biocompatibility. This study evaluates the mechanistic biocompatibility of pulpotec cement with macrophage cells (RAW 264.7) at cellular and molecular level. The biocompatibility was evaluated using experimental and computational techniques like MTT assay, oxidative stress analysis and apoptosis analysis through flow cytometry and fluorescent microscopy. The results showed concentration-dependent cytotoxicity of pulpotec cement extract to RAW 264.7 cells with an LC 50 of X/10-X/20. The computational analysis depicted the molecular interaction of pulpotec cement extract components with metabolic proteins like Sod1 and p53. The study revealed the effects of Pulpotec cement's extract, showing a concentration-dependent induction of oxidative stress and apoptosis. These effects were due to influential structural and functional abnormalities in the Sod1 and p53 proteins, caused by their molecular interaction with internalized components of Pulpotec cement. The study provided a detailed view on the utility of Pulpotec in endodontic applications, highlighting its biomedical aspects.

Perilous paradigm of graphene oxide and its derivatives in biomedical applications: Insight to immunocompatibility.

With advancements in nanotechnology and innovative materials, Graphene Oxide nanoparticles (GONP) have attracted lots of attention among the diverse types of nanomaterials owing to their distinctive physicochemical characteristics. However, the usage at scientific and industrial level has also raised concern to their toxicological interaction with biological system. Understanding these interactions is crucial for developing guidelines and recommendations for applications of GONP in various sectors, like biomedicine and environmental technologies. This review offers crucial insights and an in-depth analysis to the biological processes associated with GONP immunotoxicity with multiple cell lines including human whole blood cultures, dendritic cells, macrophages, and multiple cancer cell lines. The complicated interactions between graphene oxide nanoparticles and the immune system, are highlighted in this work, which reveals a range of immunotoxic consequences like inflammation, immunosuppression, immunostimulation, hypersensitivity, autoimmunity, and cellular malfunction. Moreover, the immunotoxic effects are also highlighted with respect to in vivo models like mice and zebrafish, insighting GO Nanoparticles' cytotoxicity. The study provides invaluable review for researchers, policymakers, and industrialist to understand and exploit the beneficial applications of GONP with a controlled measure to human health and the environment.

Nanoparticle-mediated metronomic chemotherapy in cancer: A paradigm of precision and persistence.

Current methods of cancer therapy have demonstrated enormous potential in tumor inhibition. However, a high dosage regimen of chemotherapy results in various complications which affect the normal body cells. Tumor cells also develop resistance against the prescribed drugs in the whole treatment regimen increasing the risk of cancer relapse. Metronomic chemotherapy is a modern treatment method that involves administering drugs at low doses continuously, allowing the drug sufficient time to take its effect. This method ensures that the toxicity of the drugs is to a minimum in comparison to conventional chemotherapy. Nanoparticles have shown efficacy in delivering drugs to the tumor cells in various cancer therapies. Combining nanoparticles with metronomic chemotherapy can yield better treatment results. This combination stimulates the immune system, improving cancer cells recognition by immune cells. Evidence from clinical and pre-clinical trials supports the use of metronomic delivery for drug-loaded nanoparticles. This review focuses on the functionalization of nanoparticles for improved drug delivery and inhibition of tumor growth. It emphasizes the mechanisms of metronomic chemotherapy and its conjunction with nanotechnology. Additionally, it explores tumor progression and the current methods of chemotherapy. The challenges associated with nano-based metronomic chemotherapy are outlined, paving the way for prospects in this dynamic field.

The posterity of Zebrafish in paradigm of in vivo molecular toxicological profiling.

The aggrandised advancement in utility of advanced day-to-day materials and nanomaterials has raised serious concern on their biocompatibility with human and other biotic members. In last few decades, understanding of toxicity of these materials has been given the centre stage of research using many in vitro and in vivo models. Zebrafish (Danio rerio), a freshwater fish and a member of the minnow family has garnered much attention due to its distinct features, which make it an important and frequently used animal model in various fields of embryology and toxicological studies. Given that fertilization and development of zebrafish eggs take place externally, they serve as an excellent model organism for studying early developmental stages. Moreover, zebrafish possess a comparable genetic composition to humans and share almost 70% of their genes with mammals. This particular model organism has become increasingly popular, especially for developmental research. Moreover, it serves as a link between in vitro studies and in vivo analysis in mammals. It is an appealing choice for vertebrate research, when employing high-throughput methods, due to their small size, swift development, and relatively affordable laboratory setup. This small vertebrate has enhanced comprehension of pathobiology and drug toxicity. This review emphasizes on the recent developments in toxicity screening and assays, and the new insights gained about the toxicity of drugs through these assays. Specifically, the cardio, neural, and, hepatic toxicology studies inferred by applications of nanoparticles have been highlighted.

Structural and Biochemical Studies on Klebsiella Pneumoniae Enoyl-ACP Reductase (FabI) Suggest Flexible Substrate Binding Site.

Klebsiella pneumoniae, a bacterial pathogen infamous for antibiotic resistance, is included in the priority list of pathogens by various public health organizations due to its extraordinary ability to develop multidrug resistance. Bacterial fatty acid biosynthesis pathway-II (FAS-II) has been considered a therapeutic drug target for antibacterial drug discovery. Inhibition of FAS-II enzyme, enoyl-acyl carrier protein reductase, FabI, not only inhibits bacterial infections but also reverses antibiotic resistance. Here, we characterized Klebsiella pneumoniae FabI (KpFabI) using complementary experimental approaches including, biochemical, x-ray crystallography, and molecular dynamics simulation studies. Biophysical studies shows that KpFabI organizes as a tetramer molecular assembly in solution as well as in the crystal structure. Enzyme kinetics studies reveal a distinct catalytic property towards crotonyl CoA and reducing cofactor NADH. Michaelis-Menten constant (Km) values of substrates show that KpFabI has higher preference towards NADH as compared to crotonyl CoA. The crystal structure of tetrameric apo KpFabI folds into a classic Rossman fold in which ß-strands are sandwiched between α-helices. A highly flexible substrate binding region is located toward the interior of the tetrameric assembly. Thermal stability assay on KpFabI with its substrate shows that the flexibility is primarily stabilized by cofactor NADH. Moreover, the molecular dynamics further supports that KpFabI has highly flexible regions at the substrate binding site. Together, these findings provide evidence for highly dynamic substrate binding sites in KpFabI, therefore, this information will be vital for specific inhibitors discovery targeting Klebsiella pneumoniae.

Host-directed therapy against tuberculosis: Concept and recent developments.

Tuberculosis (TB) continues to remain at the forefront of the infectious disease burden globally, albeit with some aberrations during the COVID-19 pandemic. Among many factors, the emergence of drug resistance or antimicrobial resistance (AMR) has necessitated a renewed focus on developing novel and repurposed drugs against TB. Host-directed therapy (HDT) has emerged as an attractive alternative and a complementary strategy to the conventional antibiotic-based therapy of tuberculosis since HDT enjoys the advantage of disarming the pathogen of its ability to develop drug resistance. Considering the imminent threat of AMR across the spectrum of bacterial pathogens, HDT promises to overcome the drug shortage against superbugs. While all these make HDT a very attractive strategy, identifying the right set of host targets to develop HDT remains a challenge, despite remarkable development in the field over the past decade. In this review, we examine the host mechanisms, that either inadvertently or through targeted perturbation by the pathogen, help TB pathogenesis, and we discuss the latest developments in the targeting of some of the key pathways to achieve newer TB therapeutics.

Nanotechnological interventions in bacteriocin formulations - advances, and scope for challenging food spoilage bacteria and drug-resistant foodborne pathogens.

Food spoilage bacteria (FSB) and multidrug-resistant (MDR) foodborne pathogens have emerged as one of the principal public health concerns in the twenty first century. The harmful effects of FSB lead to economic losses for the food industries. Similarly, MDR foodborne pathogens are accountable for multiple illnesses and pose a threat to consumers. Therefore, there is an urgent need to establish effective formulations for successful application against such microorganisms. In this context, the fusion of knowledge from biotechnology and nanotechnology can explore endless possibilities in the development of innovative formulations against FSB and foodborne pathogens. The current review critically examines the application of bacteriocins in the food industry and the use of nanomaterials to enhance the antimicrobial activity, stability, and precision in the target delivery of bacteriocins. This review also explores the technologies involved in the development of bacteriocin-based nanoformulations and their action against FSB and MDR foodborne pathogens, offering new possibilities in preservation technologies and addressing food safety issues in the food industry. The review highlights the challenges in the commercialization and technoeconomical feasibility of nanobacteriocin. Overall, it provides essential information and interpretation about nanotechnological advancements in bacteriocin formulation action against FSB and foodborne pathogens and future scopes.

Identification of potential flavonoid compounds as antibacterial therapeutics against Klebsiella pneumoniae infection using structure-based virtual screening and molecular dynamics simulation.

Klebsiella pneumoniae, which is among the top three pathogens on WHO's priority list, is one of the gram-negative bacteria that doctors and researchers around the world have fought for decades. Capsular polysaccharide (CPS) protein is extensively recognized as an important K. pneumoniae virulence factor. Thus, CPS has become the most characterized target for the discovery of novel drug candidates. The ineffectiveness of currently existing antibiotics urges the search for potent antimicrobial compounds. Flavonoids are a group of plant metabolites that have antibacterial potential and can enhance the present medications to elicit improved results against diverse diseases without adverse reactions. Henceforth, the present study aims to illustrate the inhibitory potential of flavonoids with varying pharmacological properties, targeting the CPS protein of K. pneumoniae by in silico approaches. The flavonoid compounds (n = 169) were retrieved from the PubChem database and screened using the structure-based virtual screening approach. Compounds with the highest binding score were estimated through their pharmacokinetic effects by ADMET descriptors. Finally, four potential inhibitors with PubChem CID: (4301534, 5213, 5481948, and 637080) were selected after molecular docking and drug-likeness analysis. All four lead compounds were employed for the MDS analysis of a 100 ns time period. Various studies were undertaken to assess the stability of the protein-ligand complexes. The binding free energy was computed using MM-PBSA, and the outcomes indicated that the molecules are having stable interactions with the binding site of the target protein. The results revealed that all four compounds can be employed as potential therapeutics against K. pneumoniae.

Posterity of nanoscience as lipid nanosystems for Alzheimer's disease regression.

Alzheimer's disease (AD) is a type of dementia that affects a vast number of people around the world, causing a great deal of misery and death. Evidence reveals a relationship between the presence of soluble Aß peptide aggregates and the severity of dementia in Alzheimer's patients. The BBB (Blood Brain Barrier) is a key problem in Alzheimer's disease because it prevents therapeutics from reaching the desired places. To address the issue, lipid nanosystems have been employed to deliver therapeutic chemicals for anti-AD therapy in a precise and targeted manner. The applicability and clinical significance of lipid nanosystems to deliver therapeutic chemicals (Galantamine, Nicotinamide, Quercetin, Resveratrol, Curcumin, HUPA, Rapamycin, and Ibuprofen) for anti-AD therapy will be discussed in this review. Furthermore, the clinical implications of the aforementioned therapeutic compounds for anti-AD treatment have been examined. Thus, this review will pave the way for researchers to fashion therodiagnostics approaches based on nanomedicine to overcome the problems of delivering therapeutic molecules across the blood brain barrier (BBB).

Intrinsic insights to antimicrobial effects of Nitrofurantoin to multi drug resistant Salmonella enterica serovar Typhimurium ms202.

Emerging multidrug resistant (MDR) serovar of Salmonella has raised the concern of their impactful effect on pathogenic infection and mortality in human lead by the enteric diseases. In order to combat the battle against these MDR Salmonella pathogen, new drug molecules need to be evaluated for their potent antibacterial application. This study evaluates the mechanistic antimicrobial effect of nitrofurantoin against a MDR strain of Salmonella named S. enterica Typhimurium ms202. The antimicrobial effect of nitrofurantoin was studied through experimental and computational approach using standard microbiological and molecular techniques like growth curve analysis, live-dead analysis, oxidative stress evaluation using high throughput techniques like flow cytometry and fluorescent microscopy. The result showed a potent dose dependent antibacterial effect of nitrofurantoin against S. enterica Typhimurium ms202 with a MIC value of 64 µg/ml. Moreover, the mechanistic excavation of the phenomenon described the mechanism as an effect of molecular interaction of nitrofurantoin molecule with membrane receptor proteins OmpC of S. enterica Typhimurium ms202 leading to internalization of the nitrofurantoin heading towards the occurrence of cellular physiological disturbances through oxidative stress impeded by nitrofurantoin-Sod1 C protein interaction. The results indicated towards a synergistic effect of membrane damage, oxidative stress and genotoxicity for the antibacterial effect of nitrofurantoin against S. enterica Typhimurium ms202. The study described the potent dose-dependent application of nitrofurantoin molecule against MDR strains of Salmonella and guided towards their use in further discovered MDR strains.

Biofilm modifiers: The disparity in paradigm of oral biofilm ecosystem.

A biofilm is a population of sessile microorganisms that has a distinct organized structure and characteristics like channels and projections. Good oral hygiene and reduction in the prevalence of periodontal diseases arise from minimal biofilm accumulation in the mouth, however, studies focusing on modifying the ecology of oral biofilms have not yet been consistently effective. The self-produced matrix of extracellular polymeric substances and greater antibiotic resistance make it difficult to target and eliminate biofilm infections, which lead to serious clinical consequences that are often lethal. Therefore, a better understanding is required to target and modify the ecology of biofilms in order to eradicate the infection, not only in instances of oral disorders but also in terms of nosocomial infections. The review focuses on several biofilm ecology modifiers to prevent biofilm infections, as well as the involvement of biofilm in antibiotic resistance, implants or in-dwelling device contamination, dental caries, and other periodontal disorders. It also discusses recent advances in nanotechnology that may lead to novel strategies for preventing and treating infections caused by biofilms as well as a novel outlook to infection control.

Atmospheric microplastic and nanoplastic: The toxicological paradigm on the cellular system.

The increasing demand for plastic in our daily lives has led to global plastic pollution. The improper disposal of plastic has resulted in a massive amount of atmospheric microplastics (MPs), which has further resulted in the production of atmospheric nanoplastics (NPs). Because of its intimate relationship with the environment and human health, microplastic and nanoplastic contamination is becoming a problem. Because microplastics and nanoplastics are microscopic and light, they may penetrate deep into the human lungs. Despite several studies demonstrating the abundance of microplastics and nanoplastics in the air, the potential risks of atmospheric microplastics and nanoplastics remain unknown. Because of its small size, atmospheric nanoplastic characterization has presented significant challenges. This paper describes sampling and characterization procedures for atmospheric microplastics and nanoplastics. This study also examines the numerous harmful effects of plastic particles on human health and other species. There is a significant void in research on the toxicity of airborne microplastics and nanoplastics upon inhalation, which has significant toxicological potential in the future. Further study is needed to determine the influence of microplastic and nanoplastic on pulmonary diseases.

Exploiting AGPase genes and encoded proteins to prioritize development of optimum engineered strains in microalgae towards sustainable biofuel production.

Although ADP glucose pyrophosphorylase (AGPase), with two large subunits (ls) and two small subunits (ss), is a promising knockout target for increasing the neutral lipid content, the details regarding the sequence-structure features and their distribution within metabolic system in microalgae is rather limited. Against this backdrop, a comprehensive genome-wide comparative analysis on 14 sequenced microalgal genomes was performed. For the first time the heterotetrameric structure of the enzyme and the interaction of the catalytic unit with the substrate was also studied. Novel findings of the present study includes: (i) at the DNA level, the genes controlling the ss are more conserved than those controlling the ls; the variation in both the gene groups is mainly due to exon number, exon length and exon phase distribution; (ii) at protein level, the ss genes are more conserved relative to those for ls; (III) three putative key consensus sequences 'LGGGAGTRLYPLTKNRAKPAV', 'WFQGTADAV' and 'ASMGIYVFRKD' were ubiquitously conserved in all the AGPases; (iv) molecular dynamics investigations revealed that the modeled AGPase heterotetrameric structure, from oleaginous algae Chlamydomonas reinharditii, was completely stable in real time environment; (v) The binding interfaces of catalytic unit, ssAGPase, from C. reinharditii with α-D-glucose 1-phosphate (αGP) was also analyzed. The results of the present study have provided system-based insights into the structure-function of the genes and encoded proteins, which provided clues for exploitation of variability in these genes that, could be further utilized to design site-specific mutagenic experiments for engineering of microalgal strains towards sustainable development of biofuel.

Designing of multi-epitope peptide vaccine against Acinetobacter baumannii through combined immunoinformatics and protein interaction-based approaches.

Acinetobacter baumannii is one of the major pathogenic ESKAPE bacterium, which is responsible for about more than 722,000 cases in a year, globally. Despite the alarming increase in multidrug resistance, a safe and effective vaccine for Acinetobacter infections is still not available. Hence in the current study, a multiepitope vaccine construct was developed using linear B cell, cytotoxic T cell, and helper T cell epitopes from the antigenic and well-conserved lipopolysaccharide assembly proteins employing systematic immunoinformatics and structural vaccinology strategies. The multi-peptide vaccine was predicted to be highly antigenic, non-allergenic, non-toxic, and cover maximum population coverage worldwide. Further, the vaccine construct was modeled along with adjuvant and peptide linkers and validated to achieve a high-quality three-dimensional structure which was subsequently utilized for cytokine prediction, disulfide engineering, and docking analyses with Toll-like receptor (TLR4). Ramachandran plot showed 98.3% of the residues were located in the most favorable and permitted regions, thereby corroborating the feasibility of the modeled vaccine construct. Molecular dynamics simulation for a 100 ns timeframe further confirmed the stability of the binding vaccine-receptor complex. Finally, in silico cloning and codon adaptation were also performed with the pET28a (+) plasmid vector to determine the efficiency of expression and translation of the vaccine. Immune simulation studies demonstrated that the vaccine could trigger both B and T cell responses and can elicit strong primary, secondary, and tertiary immune responses. The designed multi-peptide subunit vaccine would certainly expedite the experimental approach for the development of a vaccine against A. baumannii infection.

Designing a Next-Generation Multiepitope-Based Vaccine against Staphylococcus aureus Using Reverse Vaccinology Approaches.

Staphylococcus aureus is a human bacterial pathogen that can cause a wide range of symptoms. As virulent and multi-drug-resistant strains of S. aureus have evolved, invasive S. aureus infections in hospitals and the community have become one of the leading causes of mortality and morbidity. The development of novel techniques is therefore necessary to overcome this bacterial infection. Vaccines are an appropriate alternative in this context to control infections. In this study, the collagen-binding protein (CnBP) from S. aureus was chosen as the target antigen, and a series of computational methods were used to find epitopes that may be used in vaccine development in a systematic way. The epitopes were passed through a filtering pipeline that included antigenicity, toxicity, allergenicity, and cytokine inducibility testing, with the objective of identifying epitopes capable of eliciting both T and B cell-mediated immune responses. To improve vaccine immunogenicity, the final epitopes and phenol-soluble modulin α4 adjuvant were fused together using appropriate linkers; as a consequence, a multiepitope vaccine was developed. The chosen T cell epitope ensemble is expected to cover 99.14% of the global human population. Furthermore, docking and dynamics simulations were used to examine the vaccine's interaction with the Toll-like receptor 2 (TLR2), revealing great affinity, consistency, and stability between the two. Overall, the data indicate that the vaccine candidate may be extremely successful, and it will need to be evaluated in experimental systems to confirm its efficiency.

Amelioration of lipopeptide biosurfactants for enhanced antibacterial and biocompatibility through molecular antioxidant property by methoxy and carboxyl moieties.

Biosurfactants having surface-active biomolecules have been the cynosure in environment research due to their vast application. However, the lack of information about their low-cost production and detailed mechanistic biocompatibility limits the applicability. The study explores techniques for the production and design of low-cost, biodegradable, and non-toxic biosurfactants from Brevibacterium casei strain LS14 and excavates the mechanistic details of their biomedical properties like antibacterial effects and biocompatibility. Taguchi's design of experiment was used to optimize for enhancing biosurfactant production by optimal factor combinations like Waste glycerol (1%v/v), peptone (1%w/v), NaCl 0.4% (w/v), and pH 6. Under optimal conditions, the purified biosurfactant reduced the surface tension to 35 mN/m from 72.8 mN/m (MSM) and a critical micelle concentration of 25 mg/ml was achieved. Spectroscopic analyses of the purified biosurfactant using Nuclear Magnetic Resonance suggested it as a lipopeptide biosurfactant. The evaluation of mechanistic antibacterial, antiradical, antiproliferative, and cellular effects indicated the efficient antibacterial activity (against Pseudomonas aeruginosa) of biosurfactants due to free radical scavenging activity and oxidative stress. Moreover, the cellular cytotoxicity was estimated by MTT and other cellular assays revealing the phenomenon as the dose-dependent induction of apoptosis due to free radical scavenging with an LC50 of 55.6 ± 2.3 mg/ml.

Draft genome of clinical isolate Salmonella enterica Typhimurium ms204 from Odisha, India, reveals multi drug resistance and decreased virulent gene expression.

Salmonellosis, a food-borne illnesses caused by enteropathogenic bacterium Salmonella spp., is a continuous concern in both developed and developing countries. This study was carried out to perform an in-depth examination of an MDR Salmonella strain isolated from gastroenteritis patients in Odisha, India, in order to understand the genomic architecture, distribution of pathogenic island regions, and virulence factor diversity. Fecal samples were obtained from individuals with acute gastroenteritis and further subjected to panel of biochemical tests. The IlluminaHiSeq X sequencer system was used to generate whole-genome sequencing. The draft genome was submitted to gene prediction and annotation using RAST annotation system. Pathogenicity Island database and bioinformatics pipeline were used to find Salmonella pathogenicity islands (SPI) from the built scaffold. The gene expression in SPI1 and SPI2 encoded regions was investigated using qRT-PCR. The taxonomic position of Salmonella enterica subsp. enterica serovar Typhimurium was validated by serotype analysis and 16S rRNA based phylogenetic analysis. The de-novo genome assembly showed total length of 5,034,110 bp and produced 37 contigs. There are nine prophage areas, comprising of 12 regions and scaffold 8 contained a single plasmid, IncFIB. The isolate contains six known SPI genes content which was shown to be largely conserved from SPI1 to SPI2. We identified the sit ABCD cluster regulatory cascade and acquired antibiotic resistance genes in S. enterica Typhimurium ms204. Further research may aid in the correct diagnosis and monitoring of MDR Salmonella strains with a variety of physiological activities.