Comprehensive in vitro and in vivo evaluation of therapeutic potential of Bacopa-derived asiatic acid against a human oral pathogen Streptococcus mutans.

Dental caries is a common human oral disease worldwide, caused by an acid-producing bacteria Streptococcus mutans. The use of synthetic drugs and antibiotics to prevent dental caries has been increasing, but this can lead to severe side effects. To solve this issue, developing and developed countries have resorted to herbal medicines as an alternative to synthetic drugs for the treatment and prevention of dental caries. Therefore, there is an urgent need for plant-derived products to treat such diseases. Bacopa monnieri, a well-documented medicinal plant, contains 52 phytocompounds, including the pentacyclic triterpenoid metabolite known as asiatic acid (ASTA). Hence, this study aimed to demonstrate, for the first time, the antibacterial activity of phytocompound ASTA against S. mutans. The findings revealed that ASTA significantly inhibited the growth of S. mutans and the production of virulence factors such as acidurity, acidogenicity, and eDNA synthesis. Molecular docking analysis evaluated the potential activity of ASTA against S. mutans virulence genes, including VicR and GtfC. Furthermore, toxicity assessment of ASTA in human buccal epithelial cells was performed, and no morphological changes were observed. An in vivo analysis using Danio rerio (zebrafish) confirmed that the ASTA treatment significantly increased the survival rates of infected fish by hindering the intestinal colonization of S. mutans. Furthermore, the disease protection potential of ASTA against the pathognomonic symptom of S. mutans infection was proven by the histopathological examination of the gills, gut, and kidney. Overall, these findings suggest that ASTA may be a promising therapeutic and alternative drug for the treatment and prevention of oral infection imposed by S. mutans.

Network pharmacology: an efficient but underutilized approach in oral, head and neck cancer therapy-a review.

The application of network pharmacology (NP) has advanced our understanding of the complex molecular mechanisms underlying diseases, including neck, head, and oral cancers, as well as thyroid carcinoma. This review aimed to explore the therapeutic potential of natural network pharmacology using compounds and traditional Chinese medicines for combating these malignancies. NP serves as a pivotal tool that provides a comprehensive view of the interactions among compounds, genes, and diseases, thereby contributing to the advancement of disease treatment and management. In parallel, this review discusses the significance of publicly accessible databases in the identification of oral, head, and neck cancer-specific genes. These databases, including those for head and neck oral cancer, head and neck cancer, oral cancer, and genomic variants of oral cancer, offer valuable insights into the genes, miRNAs, drugs, and genetic variations associated with these cancers. They serve as indispensable resources for researchers, clinicians, and drug developers, contributing to the pursuit of precision medicine and improved treatment of these challenging malignancies. In summary, advancements in NP could improve the globalization and modernization of traditional medicines and prognostic targets as well as aid in the development of innovative drugs. Furthermore, this review will be an eye-opener for researchers working on drug development from traditional medicines by applying NP approaches.

Deciphering the Potential Therapeutic Effects of Hydnocarpus wightianus Seed Extracts using in vitro and in silico approaches.

Phytocompounds possess the potential to treat a broad spectrum of disorders due to their remarkable bioactivity. Naturally occurring compounds possess lower toxicity profiles, which making them attractive targets for drug development. Hydnocarpus wightianus seeds were extracted using ethanol, acetone, and hexane solvents. The extracts were evaluated for phytochemicals screening and other therapeutic characteristics, such as free radicals scavenging, anti α-amylase, anti α-glucosidase, and anti-bacterial activities. The ethanolic extract exhibited noteworthy antibacterial characteristics and demonstrated considerable antioxidant, and anti-diabetic effects. The IC50 value of the ethanolic extract for Dpph, α-amylase, and α-glucosidase were found to be 77.299 ± 3.381 µg/mL, 165.56 2.56 µg/mL, and 136.58 ± 5.82 µg/mL, respectively. The ethanolic extract was effective against Methicillin resistant Staphylococcus aureus (26 mm zone of inhibition at 100 µL concentration). Molecular docking investigations revealed the phytoconstituent's inhibitory mechanisms against diabetic, free radicals, and bacterial activity. Docking score for phytocompounds against targeted protein varies from -7.2 to -5.1 kcal/mol. The bioactive compounds present in the ethanolic extract were identified by Gas chromatography/Mass spectrometry analysis, followed by molecular docking and molecular dynamic simulation studies to further explore the phytoconstituent's inhibitory mechanism of α-glucosidase, ∝-amylase, radical scavenging, and bacterial activity. The electronic structure and possible pharmacological actions of the phytocompound were revealed through the use of Density Functional Theory (DFT) analysis. Computational and in vitro studies revealed that these identified compounds have anti-diabetic, anti-oxidant, and anti-bacterial activities against antibiotic-resistant strain of Staphylococcus aureus.

Methyl jasmonate and salicylic acid as powerful elicitors for enhancing the production of secondary metabolites in medicinal plants: an updated review.

Plant secondary metabolites are bioactive scaffolds that are crucial for plant survival in the environment and to maintain a defense mechanism from predators. These compounds are generally present in plants at a minimal level and interestingly, they are found to have a wide variety of therapeutic values for humans. Several medicinal plants are used for pharmaceutical purposes due to their affordability, fewer adverse effects, and vital role in traditional remedies. Owing to this reason, these plants are exploited at a high range worldwide and therefore many medicinal plants are on the threatened list. There is a need of the hour to tackle this major problem, one effective approach called elicitation can be used to enhance the level of existing and novel plant bioactive compounds using different types of elicitors namely biotic and abiotic. This process can be generally achieved by in vitro and in vivo experiments. The current comprehensive review provides an overview of biotic and abiotic elicitation strategies used in medicinal plants, as well as their effects on secondary metabolites enhancement. Further, this review mainly deals with the enhancement of biomass and biosynthesis of different bioactive compounds by methyl jasmonate (MeJA) and salicylic acid (SA) as elicitors of wide medicinal plants in in vitro by using different cultures. The present review was suggested as a significant groundwork for peers working with medicinal plants by applying elicitation strategies along with advanced biotechnological approaches.

Application of CRISPR/Cas system in cereal improvement for biotic and abiotic stress tolerance.

MAIN CONCLUSION: Application of the recently developed CRISPR/Cas tools might help enhance cereals' growth and yield under biotic and abiotic stresses. Cereals are the most important food crops for human life and an essential source of nutrients for people in developed and developing countries. The growth and yield of all major cereals are affected by both biotic and abiotic stresses. To date, molecular breeding and functional genomic studies have contributed to the understanding and improving cereals' growth and yield under biotic and abiotic stresses. Clustered, regularly inter-spaced, short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system has been predicted to play a major role in precision plant breeding and developing non-transgenic cereals that can tolerate adverse effects of climate change. Variants of next-generation CRISPR/Cas tools, such as prime editor, base editor, CRISPR activator and repressor, chromatin imager, Cas12a, and Cas12b, are currently used in various fields, including plant science. However, few studies have been reported on applying the CRISPR/Cas system to understand the mechanism of biotic and abiotic stress tolerance in cereals. Rice is the only plant used frequently for such studies. Genes responsible for biotic and abiotic stress tolerance have not yet been studied by CRISPR/Cas system in other major cereals (sorghum, barley, maize and small millets). Examining the role of genes that respond to biotic and abiotic stresses using the CRISPR/Cas system may help enhance cereals' growth and yield under biotic and abiotic stresses. It will help to develop new and improved cultivars with biotic- and abiotic-tolerant traits for better yields to strengthen food security. This review provides information for cereal researchers on the current status of the CRISPR/Cas system for improving biotic and abiotic stress tolerance in cereals.

Conventional and Omics Approaches for Understanding the Abiotic Stress Response in Cereal Crops-An Updated Overview.

Cereals have evolved various tolerance mechanisms to cope with abiotic stress. Understanding the abiotic stress response mechanism of cereal crops at the molecular level offers a path to high-yielding and stress-tolerant cultivars to sustain food and nutritional security. In this regard, enormous progress has been made in the omics field in the areas of genomics, transcriptomics, and proteomics. Omics approaches generate a massive amount of data, and adequate advancements in computational tools have been achieved for effective analysis. The combination of integrated omics and bioinformatics approaches has been recognized as vital to generating insights into genome-wide stress-regulation mechanisms. In this review, we have described the self-driven drought, heat, and salt stress-responsive mechanisms that are highlighted by the integration of stress-manipulating components, including transcription factors, co-expressed genes, proteins, etc. This review also provides a comprehensive catalog of available online omics resources for cereal crops and their effective utilization. Thus, the details provided in the review will enable us to choose the appropriate tools and techniques to reduce the negative impacts and limit the failures in the intensive crop improvement study.

Assessing the Anti-inflammatory Effects of Bacopa-Derived Bioactive Compounds Using Network Pharmacology and In Vitro Studies.

Bacopa monnieri is reported as a potent Indian medicinal plant that possesses numerous pharmacological activities due to the presence of various bioactive compounds. These pharmacological activities were used in the ancient medicine system to cure inflammatory conditions. Bacopa has the ability to reduce acute pain and inflammation by inhibiting the enzyme cyclo-oxygenase-2 (COX-2) and reducing COX-2-arbitrated prostanoid mediators. Moreover, the anti-inflammatory property may also be associated with the neuroprotective activity of Bacopa. Considering this importance, the current pilot study focused on the anti-inflammatory potential of various phytocompounds of bacopa and their interaction with inflammation responsible genes such as COX2, iNOS, LOX, STAT3, CCR1, and MMP9 through pharmacology analysis of its systems. Docking results revealed that, quercetin (QR) showed significant binding energies with inflammatory genes. Hence, we selected QR as a potential phytocompound for further in vitro experiments. This existing study aimed to evaluate the efficacy of QR as a potent anti-inflammatory compound against lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The in vitro analysis concludes that QR effectively reduces the production of nitric oxide (NO) in LPS-induced RAW264.7 cells and downregulates the expression of COX-2 and iNOS genes due to the inhibitory potential of QR on LPS-stimulated NO production.

Transcriptomics, Cheminformatics, and Systems Pharmacology Strategies Unveil the Potential Bioactives to Combat COVID-19.

Coronavirus disease (COVID-19) is a viral disease caused by the SARS-CoV-2 virus and is becoming a global threat again because of the higher transmission rate and lack of proper therapeutics as well as the rapid mutations in the genetic pattern of SARS-CoV-2. Despite vaccinations, the prevalence and recurrence of this infection are still on the rise, which urges the identification of potential global therapeutics for a complete cure. Plant-based alternative medicine is becoming popular worldwide because of its higher efficiency and minimal side effects. Yet, identifying the potential medicinal plants and formulating a plant-based medicine is still a bottleneck. Hence, in this study, the systems pharmacology, transcriptomics, and cheminformatics approaches were employed to uncover the multi-targeted mechanisms and to screen the potential phytocompounds from significant medicinal plants to treat COVID-19. These approaches have identified 30 unique COVID-19 human immune genes targeted by the 25 phytocompounds present in four selected ethnobotanical plants. Differential and co-expression profiling and pathway enrichment analyses delineate the molecular signaling and immune functional regulations of the COVID-19 unique genes. In addition, the credibility of these compounds was analyzed by the pharmacological features. The current holistic finding is the first to explore whether the identified potential bioactives could reform into a drug candidate to treat COVID-19. Furthermore, the molecular docking analysis was employed to identify the important bioactive compounds; thus, an ultimately significant medicinal plant was also determined. However, further laboratory evaluation and clinical validation are required to determine the efficiency of a therapeutic formulation against COVID-19.

Multi-Omics and Integrative Approach towards Understanding Salinity Tolerance in Rice: A Review.

Rice (Oryza sativa L.) plants are simultaneously encountered by environmental stressors, most importantly salinity stress. Salinity is the major hurdle that can negatively impact growth and crop yield. Understanding the salt stress and its associated complex trait mechanisms for enhancing salt tolerance in rice plants would ensure future food security. The main aim of this review is to provide insights and impacts of molecular-physiological responses, biochemical alterations, and plant hormonal signal transduction pathways in rice under saline stress. Furthermore, the review highlights the emerging breakthrough in multi-omics and computational biology in identifying the saline stress-responsive candidate genes and transcription factors (TFs). In addition, the review also summarizes the biotechnological tools, genetic engineering, breeding, and agricultural practicing factors that can be implemented to realize the bottlenecks and opportunities to enhance salt tolerance and develop salinity tolerant rice varieties. Future studies pinpointed the augmentation of powerful tools to dissect the salinity stress-related novel players, reveal in-depth mechanisms and ways to incorporate the available literature, and recent advancements to throw more light on salinity responsive transduction pathways in plants. Particularly, this review unravels the whole picture of salinity stress tolerance in rice by expanding knowledge that focuses on molecular aspects.

Unraveling the multi-targeted curative potential of bioactive molecules against cervical cancer through integrated omics and systems pharmacology approach.

Molecular level understanding on the role of viral infections causing cervical cancer is highly essential for therapeutic development. In these instances, systems pharmacology along with multi omics approach helps in unraveling the multi-targeted mechanisms of novel biologically active compounds to combat cervical cancer. The immuno-transcriptomic dataset of healthy and infected cervical cancer patients was retrieved from the array express. Further, the phytocompounds from medicinal plants were collected from the literature. Network Analyst 3.0 has been used to identify the immune genes around 384 which are differentially expressed and responsible for cervical cancer. Among the 87 compounds reported in plants for treating cervical cancer, only 79 compounds were targeting the identified immune genes of cervical cancer. The significant genes responsible for the domination in cervical cancer are identified in this study. The virogenomic signatures observed from cervical cancer caused by E7 oncoproteins serve as the potential therapeutic targets whereas, the identified compounds can act as anti-HPV drug deliveries. In future, the exploratory rationale of the acquired results will be useful in optimizing small molecules which can be a viable drug candidate.

Jasmonates in plant growth and development and elicitation of secondary metabolites: An updated overview.

Secondary metabolites are incontestably key specialized molecules with proven health-promoting effects on human beings. Naturally synthesized secondary metabolites are considered an important source of pharmaceuticals, food additives, cosmetics, flavors, etc., Therefore, enhancing the biosynthesis of these relevant metabolites by maintaining natural authenticity is getting more attention. The application of exogenous jasmonates (JAs) is well recognized for its ability to trigger plant growth and development. JAs have a large spectrum of action that covers seed germination, hypocotyl growth regulation, root elongation, petal expansion, and apical hook growth. This hormone is considered as one of the key regulators of the plant's growth and development when the plant is under biotic or abiotic stress. The JAs regulate signal transduction through cross-talking with other genes in plants and thereby deploy an appropriate metabolism in the normal or stressed conditions. It has also been found to be an effective chemical elicitor for the synthesis of naturally occurring secondary metabolites. This review discusses the significance of JAs in the growth and development of plants and the successful outcomes of jasmonate-driven elicitation of secondary metabolites including flavonoids, anthraquinones, anthocyanin, xanthonoid, and more from various plant species. However, as the enhancement of these metabolites is essentially measured via in vitro cell culture or foliar spray, the large-scale production is significantly limited. Recent advancements in the plant cell culture technology lay the possibilities for the large-scale manufacturing of plant-derived secondary metabolites. With the insights about the genetic background of the metabolite biosynthetic pathway, synthetic biology also appears to be a potential avenue for accelerating their production. This review, therefore, also discussed the potential manoeuvres that can be deployed to synthesis plant secondary metabolites at the large-scale using plant cell, tissue, and organ cultures.

Global Integrated Genomic and Transcriptomic Analyses of MYB Transcription Factor Superfamily in C3 Model Plant Oryza sativa (L.) Unravel Potential Candidates Involved in Abiotic Stress Signaling.

Plant transcription factors (TFs) are significant players in transcriptional regulations, signal transduction, and constitute an integral part of signaling networks. MYB TFs are major TF superfamilies that play pivotal roles in regulation of transcriptional reprogramming, physiological processes, and abiotic stress (AbS) responses. To explore the understanding of MYB TFs, genome and transcriptome-wide identification was performed in the C3 model plant, Oryza sativa (OsMYB). This study retrieved 114 OsMYB TFs that were computationally analyzed for their expression profiling, gene organization, cis-acting elements, and physicochemical properties. Based on the microarray datasets, six OsMYB genes which were sorted out and identified by a differential expression pattern were noted in various tissues. Systematic expression profiling of OsMYB TFs showed their meta-differential expression of different AbS treatments, spatio-temporal gene expression of various tissues and their growth in the field, and gene expression profiling in responses to phytohormones. In addition, the circular ideogram of OsMYB genes in related C4 grass plants conferred the gene synteny. Protein-protein interactions of these genes revealed the molecular crosstalk of OsMYB TFs. Transcriptional analysis (qPCR) of six OsMYB players in response to drought and salinity stress suggested the involvement in individual and combined AbS responses. To decipher how these OsMYB play functional roles in AbS dynamics, further research is a prerequisite.

Vitex negundo L. derived specialized molecules unveil the multi-targeted therapeutic avenues against COPD: a systems pharmacology approach.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease caused by increasing breathing passage obstruction which completely disrupts human homeostasis. Some patients require lung transplantation or long-term oxygen therapy. COPD is one of the noxious diseases and its fourth leading cause of death around the globe. There is an immediate need for potential drug development to tackle this serious disease. Folk medicines are used to combat complex diseases that have shown effectiveness in the treatment of breathing diseases. Vitex negundo L. is an ethnobotanically important medicinal plant used for various ailments and modulates human cellular events. This shrub has diverse specialized metabolites and is being used as complementary medicine in various countries. Though systems-level understanding is there on the mode of action, the multi-target treatment strategy for COPD is still a bottleneck. METHODS: In this investigation, systems pharmacology, cheminformatics, and molecular docking analyses were performed to unravel the multi-targeted mechanisms of V. negundo L. potential bioactives to combat COPD. RESULTS: Cheminformatics analysis combined with the target mining process identified 86 specialized metabolites and their corresponding 1300 direct human receptors, which were further imputed and validated systematically. Furthermore, molecular docking approaches were employed to evaluate the potential activity of identified potential compounds. In addition, pharmacological features of these bioactives were compared with available COPD drugs to recognize potential compounds that were found to be more efficacious with higher bioactive scores. CONCLUSIONS: The present study unravels the druggable targets and identifies the bioactive compounds present in V. negundo L., that may be utilized for potential treatment against COPD. However, further in vivo analyses and clinical trials of these molecules are essential to deciphering their efficacy.

Molecular Insights into Freezing Stress in Peach Based on Multi-Omics and Biotechnology: An Overview.

In nature or field conditions, plants are frequently exposed to diverse environmental stressors. Among abiotic stresses, the low temperature of freezing conditions is a critical factor that influences plants, including horticultural crops, decreasing their growth, development, and eventually quality and productivity. Fortunately, plants have developed a mechanism to improve the tolerance to freezing during exposure to a range of low temperatures. In this present review, current findings on freezing stress physiology and genetics in peach (Prunus persica) were refined with an emphasis on adaptive mechanisms for cold acclimation, deacclimation, and reacclimation. In addition, advancements using multi-omics and genetic engineering approaches unravel the molecular physiological mechanisms, including hormonal regulations and their general perceptions of freezing tolerance in peach were comprehensively described. This review might pave the way for future research to the horticulturalists and research scientists to overcome the challenges of freezing temperature and improvement of crop management in these conditions.

Plant Derived Bioactive Compounds, Their Anti-Cancer Effects and In Silico Approaches as an Alternative Target Treatment Strategy for Breast Cancer: An Updated Overview.

Cancer is one of the most common malignant diseases that occur worldwide, among which breast cancer is the second leading cause of death in women. The subtypes are associated with differences in the outcome and were selected for treatments according to the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor. Triple-negative breast cancer, one of the subtypes of breast cancer, is difficult to treat and can even lead to death. If breast cancer is not treated during the initial stages, it may spread to nearby organs, a process called metastasis, through the blood or lymph system. For in vitro studies, MCF-7, MDA-MB-231, MDA-MB-468, and T47B are the most commonly used breast cancer cell lines. Clinically, chemotherapy and radiotherapy are usually expensive and can also cause side effects. To overcome these issues, medicinal plants could be the best alternative for chemotherapeutic drugs with fewer side effects and cost-effectiveness. Furthermore, the genes involved in breast cancer can be regulated and synergized with signaling molecules to suppress the proliferation of breast cancer cells. In addition, nanoparticles encapsulating (nano-encapsulation) medicinal plant extracts showed a significant reduction in the apoptotic and cytotoxic activities of breast cancer cells. This present review mainly speculates an overview of the native medicinal plant derived anti-cancerous compounds with its efficiency, types and pathways involved in breast cancer along with its genes, the mechanism of breast cancer brain metastasis, chemoresistivity and its mechanism, bioinformatics approaches which could be an effective alternative for drug discovery.

Seed Dormancy and Pre-Harvest Sprouting in Rice-An Updated Overview.

Pre-harvest sprouting is a critical phenomenon involving the germination of seeds in the mother plant before harvest under relative humid conditions and reduced dormancy. As it results in reduced grain yield and quality, it is a common problem for the farmers who have cultivated the rice and wheat across the globe. Crop yields need to be steadily increased to improve the people's ability to adapt to risks as the world's population grows and natural disasters become more frequent. To improve the quality of grain and to avoid pre-harvest sprouting, a clear understanding of the crops should be known with the use of molecular omics approaches. Meanwhile, pre-harvest sprouting is a complicated phenomenon, especially in rice, and physiological, hormonal, and genetic changes should be monitored, which can be modified by high-throughput metabolic engineering techniques. The integration of these data allows the creation of tailored breeding lines suitable for various demands and regions, and it is crucial for increasing the crop yields and economic benefits. In this review, we have provided an overview of seed dormancy and its regulation, the major causes of pre-harvest sprouting, and also unraveled the novel avenues to battle pre-harvest sprouting in cereals with special reference to rice using genomics and transcriptomic approaches.

RNA-Seq based global transcriptome analysis of rice unravels the key players associated with brown planthopper resistance.

Rice production is adversely affected by biotic and abiotic stresses. Among the biotic stresses, brown planthopper (BPH) majorly affects the rice yield. Comprehending the genome and candidate players is essential for the resistance to BPH. This holistic study aimed to dissect the complex BPH resistance mechanism of the host against pathogen. Transcriptome analysis of six samples comprising of two-resistant (PTB33, BM71) and one-sensitive (TN1) genotypes under control and stress conditions was carried-out. A total of 148 million filtered reads were generated after quality check. Among these, 127 million filtered reads were aligned to the rice genome. These aligned reads were taken for further analysis. A total of 14,358 DEGs across the genotypes under stress were identified. Of which, 4820 DEGs were functionally annotated from 9266 uniquely mapped DEGs. Fifty-five potential BPH stress players were selected from the in-silico analysis of DEGs. qRT-PCR results revealed key players were differentially regulated in both resistant and sensitive genotypes. Spatio-temporal and hormone level expression signature of 55 BPH associated players were analyzed and noted their differential expression in tissues and hormones, respectively. This study inferred the significant differences in gene expression signatures may contribute to the process of BPH resistance mechanism in rice.

An Overview of Abiotic Stress in Cereal Crops: Negative Impacts, Regulation, Biotechnology and Integrated Omics.

Abiotic stresses (AbS), such as drought, salinity, and thermal stresses, could highly affect the growth and development of plants. For decades, researchers have attempted to unravel the mechanisms of AbS for enhancing the corresponding tolerance of plants, especially for crop production in agriculture. In the present communication, we summarized the significant factors (atmosphere, soil and water) of AbS, their regulations, and integrated omics in the most important cereal crops in the world, especially rice, wheat, sorghum, and maize. It has been suggested that using systems biology and advanced sequencing approaches in genomics could help solve the AbS response in cereals. An emphasis was given to holistic approaches such as, bioinformatics and functional omics, gene mining and agronomic traits, genome-wide association studies (GWAS), and transcription factors (TFs) family with respect to AbS. In addition, the development of omics studies has improved to address the identification of AbS responsive genes and it enables the interaction between signaling pathways, molecular insights, novel traits and their significance in cereal crops. This review compares AbS mechanisms to omics and bioinformatics resources to provide a comprehensive view of the mechanisms. Moreover, further studies are needed to obtain the information from the integrated omics databases to understand the AbS mechanisms for the development of large spectrum AbS-tolerant crop production.

Staphyloxanthin inhibitory potential of thymol impairs antioxidant fitness, enhances neutrophil mediated killing and alters membrane fluidity of methicillin resistant Staphylococcus aureus.

Staphylococcus aureus is a leading pathogen responsible for mild to severe invasive infections in humans. Especially, methicillin resistant Staphylococcus aureus (MRSA) is prevalent in hospital and community associated infections. Staphyloxanthin is a golden yellow color eponymous pigment produced by S. aureus and provides resistance to reactive oxygen species (ROS) and host neutrophil-based killing. In addition, this membrane pigment contributes to membrane rigidity and helps MRSA to survive under stress conditions. Targeting virulence of pathogen without exerting selection pressure is the recent approach to fight bacterial infections without developing drug resistance. The present study for the first time evaluated the staphyloxanthin inhibitory potential of thymol against MRSA. Qualitative and quantitative analyses demonstrated 90% of staphyloxanthin inhibition at 100 µg/mL concentration of thymol without alteration in growth. Molecular docking analysis and in vitro measurement of metabolic intermediates of staphyloxanthin revealed that thymol could possibly interact with CrtM to inhibit staphyloxanthin. Absorbance and infra red spectra further validated the inhibition of staphyloxanthin by thymol. In addition, thymol treatment significantly reduced the resistance of MRSA to ROS and neutrophil-based killing as exhibited by oxidant susceptibility assays and ex vivo innate immune clearance assay using human whole blood and neutrophils. Further, reduction in staphyloxanthin by thymol treatment increased the membrane fluidity and made MRSA cells more susceptible to membrane targeting antibiotic polymyxin B. Especially, thymol was found to be non-cytotoxic to human peripheral blood mononuclear cells. Our study validated the antivirulence potential of thymol against MRSA by inhibiting staphyloxanthin and suggests the prospective therapeutic role of thymol to combat MRSA infections.

Global transcriptome analysis of novel stress associated protein (SAP) genes expression dynamism of combined abiotic stresses in Oryza sativa (L.).

Genes encoding proteins with A20/AN1 zinc-finger domains, belonging to the stress associated protein (SAP) gene family, are present in all eukaryotes and play a decisive role in plant response to diverse physiological and molecular activities particularly on biotic and abiotic stresses (AbS). In this first and foremost study, global transcriptome analysis of members of the SAP gene family was carried out in C3 model-Oryza sativa (OsSAP) aiming at the identification of OsSAP genes activated in response to unique or Combined AbS (CAbS). Based on the available spatio-temporal and phytohormonal RNA-Seq expression profile datasets, nine OsSAP genes were filtered out and identified by a differential expression signature noted in various tissues as well as plant hormones. Comparative genome ideogram of OsSAP genes confirmed the orthologous collinearity with C4 panicoid genomes. Interactome of these genes, revealed the molecular cross-talks of OsSAP. Thus, the computational expression signature of OsSAP genes led to a better understanding of gene dynamism in diverse developmental tissues/organs. Transcriptional regulation analysis of key OsSAP genes in response to stress (drought and salinity) suggested the novel role of OsSAP1, OsSAP2, OsSAP5, OsSAP7, OsSAP8 and OsSAP11 in AbS. Altogether, the study provides deeper insights on molecular characteristics of OsSAP genes, which could be deployed further to decipher their precise functional roles in AbS responses.Communicated by Ramaswamy H. Sarma.