Renu Chaudhary

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

ABSTRACT 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.

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

Abstract 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.

Escherichia coli as a Potential Candidate Against Food Borne Bacterial Infections

The expanding familiarity with the dangers emanating from food-related pathogens as well as from the counterfeit synthetic additives used to control them has prompted restored enthusiasm for supposed ‘green advances’ including novel approaches for a minimal processing and exploitation of commensal bacterial strains as a source of novel antibacterial agents or in an alternative as a probiotic. The present article demonstrates detailed analysis of extracellularly released and intracellular proteins of non-pathogenic bacterial strains residing in human gut against pathogens involved in food-borne illness and toxication. Among the human microbiota, the cytosolic proteins of Escherichia coli DH5α (being a prominent and primitive bacterial species in human gut) have been found to be most active against Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Proteus vulgaris, Salmonella typhi and Vibrio cholerae (the major food-borne pathogens) showing minimum inhibitory concentration (MIC) in the range of 62.50–250.0 μg/ml using resazurin-based microtitre dilution method. In disc diffusion assay, the MIC was found to be in the range of 6.25–25 μg/disc. Hence, Escherichia coli DH5α emerges as a source of novel antimicrobial proteins.

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.

Protein Therapeutic: Production, Application, and Future Scenario

The demands for recombinant therapeutic proteins are escalating rapidly over the past two decades because of its effectiveness in treating human diseases that are uncurable. To meet the increasing demand, there is continuous need to enhance the existing expression systems, furthermore building up an attractive strategy to confront the therapeutic protein demands. Nowadays, human cell line has come up as a novel and effective strategy to generate therapeutic proteins since this expression framework possesses the machinery to modify the recombinant proteins to its final form (posttranslational modifications) analogous to those present human proteins. In addition human cell lines also decrease the possible immunogenicity against non-human antigenic determinants. Therefore, the present chapter discusses about how recombinant proteins with therapeutic properties can be in mammalian cells and their application, and finally we will talk how new innovations might add to the further advancement and generation of therapeutic proteins.