Finger Millet (Eleusine coracana) Plant-Endophyte Dynamics: Plant Growth, Nutrient Uptake, and Zinc Biofortification.

Endophytic fungi and bacteria were isolated from finger millet and their effects on finger millet growth parameters and zinc and NPK contents in grains were studied. Out of 70 fungal and 112 bacterial endophytes, the two best fungal and bacterial isolates were selected on the basis of zinc solubilization and plant-growth-promoting attributes. The fungal isolates identified were Aspergillus terreus and Lecanicillium sp., and the bacterial isolates were Pseudomonas bijieensis and Priestia megaterium. The endophytic zinc, NPK mobilization, and plant-growth-promoting efficacy were determined in a pot experiment with zinc carbonate as the zinc source. Endophytic-primed plants showed enhanced shoot and root lengths compared to the unprimed control. Endophytes increased the zinc content in grains by between 12.12% and 18.80% compared to control plants. Endophytes also augmented the NPK concentrations in seeds compared to control plants and exhibited stability in a diverse range of pHs, temperatures, and NaCl concentrations, and exhibited growth on various carbohydrate and nitrogen sources. This is the first study reporting the interaction of Aspergillus terreus, Lecanicillium sp., Pseudomonas bijieensis, and Priestia megaterium with finger millet for grain Zn biofortification and NPK concentration enhancement. This study indicated that zinc-dissolving endophytes possess the potential for enhancing the zinc and NPK content in grains in addition to the plant-growth-promoting attributes.

Advances in tuberculous meningitis diagnosis.

Introduction: Tuberculous meningitis (TBM) is the most devastating form of central nervous system tuberculosis (TB) and causes high mortality worldwide. Nonspecific clinical manifestations and limited sensitivity of existing laboratory methods make the diagnosis elusive due to the paucibacillary nature of the infection. Areas Covered: We reviewed current literature on the adequacy and limitations of globally existing laboratory methods for diagnosing TBM. Expert opinion: TBM is deadliest among all TB forms, as the outcome may lead to death in 50% of cases, and survivors undergo irreversible neurological disorders. Therefore, early diagnosis and prompt treatment are cornerstones of effective disease management. Conventional microscopy and culture are widely used modalities but remain inadequate in most TBM cases. Although expanded use of rapid molecular tests such as real-time PCR and Xpert Ultra, even in resource-limited settings, hold promising results for TB diagnosis but need optimization for early detection of TBM. Moreover, CSF IGRA is also used but unable to differentiate between active and latent TB. Overall no single test for diagnosing TBM has adequate accuracy so, there is an urgent need to devise a point-of-care test.

In Silico Protein Interaction Network Analysis of Virulence Proteins Associated with Invasive Aspergillosis for Drug Discovery.

BACKGROUND: Protein-Protein interaction (PPI) network analysis of virulence proteins of Aspergillus fumigatus is a prevailing strategy to understand the mechanism behind the virulence of A. fumigatus. The identification of major hub proteins and targeting the hub protein as a new antifungal drug target will help in treating the invasive aspergillosis. MATERIALS & METHOD: In the present study, the PPI network of 96 virulence (drug target) proteins of A. fumigatus were investigated which resulted in 103 nodes and 430 edges. Topological enrichment analysis of the PPI network was also carried out by using STRING database and Network analyzer a cytoscape plugin app. The key enriched KEGG pathway and protein domains were analyzed by STRING. CONCLUSION: Manual curation of PPI data identified three proteins (PyrABCN-43, AroM-34, and Glt1- 34) of A. fumigatus possessing the highest interacting partners. Top 10% hub proteins were also identified from the network using cytohubba on the basis of seven algorithms, i.e. betweenness, radiality, closeness, degree, bottleneck, MCC and EPC. Homology model and the active pocket of top three hub proteins were also predicted.

The Sesamum indicum Rhizosphere Associated Bacterium: A Source of Antifungal Compound.

BACKGROUND: The impact of fungal infections on human health has increased considerably within a past few decades. Although drugs with antifungal properties are available, but they are less effective and are associated with side effects. OBJECTIVE AND METHOD: To screen the bacterial isolates from Sesamum indicum and to investigate the antifungal activity of the screened bacterial isolates against Aspergillus sp. Co-culture assay and agar overlay were used to scrutinize the anti-Aspergillus activity. Furthermore, optimization of media and growth conditions to enhance the production of anti-Aspergillus compound. RESULTS: Several bacterial cultures were isolated from Sesamum indicum rhizosphere collected from Mandi (H.P.) India. These bacterial cultures were assayed for antifungal activity against Aspergillus species i.e. A. fumigatus and A. niger. Two most potent strains were chosen for more detailed analyses. The biochemical characterization and 16S ribosomal RNA sequencing revealed that Burkholderia sp. strain RC1 and Acinetobacter pittii strain RC2 exhibit strong similarity (100%) with Burkholderia sp. SR2-07 and Acinetobacter sp. strain 3-59. Additionally, it was also validated that RC1 and RC2 showed significant difference in the production of anti-Aspergillusactivity under altered growth conditions. CONCLUSION: Results from this study recommend that plant rhizosphere remains a rich hotspot for delivering a novel antifungal compounds.

Siderophores; iron scavengers: the novel & promising targets for pathogen specific antifungal therapy.

INTRODUCTION: The recent emergence of resistance, toxicity paradigm and limited efficacy of conventional antifungal drugs necessitate the identification of de novo targets in fungal metabolism. One of the most critical physiological processes during in vivo pathogenesis is maintenance of iron homeostasis. The most life threatening opportunistic human fungal pathogens like Aspergillus, Candida and Cryptococcus exploit the siderophore mediated iron uptake mechanism either for survival, virulence, propagation or resistance to oxidative stress envisaged in vivo during infection. Areas covered: In this review, we will highlight the metabolic pathways; specifically siderophore biosynthesis, uptake and utilisation, triggered in the fungal pathogens in iron starving conditions and the various putative targets viable in these pathways to be recruited as novel therapeutic antidotes either via biosynthetic enzymes catalytic site inhibitors or as drug conjugates through trojan horse approach and further role in the development of fungal specific reliable diagnostic markers. Expert opinion: Siderophores are the weapons released by a pathogen to conquer the battle for iron acquisition. Hence, the fungal siderophore biosynthetic pathways along with their uptake and utilisation mechanisms represent an ideal target for pathogen specific, host friendly therapeutic strategy which would block the proliferation of parasite without causing any harm to the mammalian host.

Perspectives on Phytochemicals as Antibacterial Agents: An Outstanding Contribution to Modern Therapeutics.

Despite the considerable advancements in the development of antimicrobial agents, incidents of epidemics due to multi drug resistance in microorganisms have created a massive hazard to mankind. Due to increased resistance against conventional antibiotics, researchers and pharmaceutical industries are more concerned about novel therapeutic agents for the prevention of bacterial infections. Enormous wealth of traditional system of medicine gains importance in health therapies over again. With ancient credentials of potent medicinal plants, various herbal remedies came forward for the management of bacterial infections. The Ayurvedic approach facilitates the development of new therapeutic agents due to structural and functional diversity among phytochemicals. The abundance and diversity is responsible for the characterization of new lead structures from medicinal plants. Industrial interest has increased due to recent research advancements viz. synergistic and high-throughput screening approach for the evaluation of vast variety of phytochemicals. The review certainly emphasizes on the traditional medicines as alternatives to conventional chemotherapeutic drugs. The review briefly describes mode of action of various antibiotics and resistance mechanisms. This review focuses on the chemical diversity and various mechanisms of action of phytochemicals against bacterial pathogens.

Silver(I)-Promoted ipso-Nitration of Carboxylic Acids by Nitronium Tetrafluoroborate.

A novel and efficient method for the regioselective nitration of a series of aliphatic and aromatic carboxylic acids to their corresponding nitro compounds using nitronium tetrafluoroborate and silver carbonate in dimethylacetamide has been described. This transformation is believed to proceed via the alkyl-silver or aryl-silver intermediate, which subsequently reacts with the nitronium ion to form nitro substances. Mild reaction conditions, tolerant of a broad range of functional groups, and formation of only the ipso-nitrated products are the key features of this methodology when compared to known methods for syntheses of nitroalkyls and nitroarenes.

Role of single nucleotide polymorphisms in pharmacogenomics and their association with human diseases.

Global statistical data shed light on an alarming trend that every year thousands of people die due to adverse drug reactions as each individual responds in a different way to the same drug. Pharmacogenomics has come up as a promising field in drug development and clinical medication in the past few decades. It has emerged as a ray of hope in preventing patients from developing potentially fatal complications due to adverse drug reactions. Pharmacogenomics also minimizes the exposure to drugs that are less/non-effective and sometimes even found toxic for patients. It is well reported that drugs elicit different responses in different individuals due to variations in the nucleotide sequences of genes encoding for biologically important molecules (drug-metabolizing enzymes, drug targets and drug transporters). Single nucleotide polymorphisms (SNPs), the most common type of polymorphism found in the human genome is believed to be the main reason behind 90% of all types of genetic variations among the individuals. Therefore, pharmacogenomics may be helpful in answering the question as to how inherited differences in a single gene have a profound effect on the mobilization and biological action of a drug. In the present review, we have discussed clinically relevant examples of SNP in associated diseases that can be utilized as markers for "better management of complex diseases" and attempted to correlate the drug response with genetic variations. Attention is also given towards the therapeutic consequences of inherited differences at the chromosomal level and how associated drug disposition and/or drug targets differ in various diseases as well as among the individuals.