The recognition of unusual yeasts as an agent of life-threatening infection and their intrinsic resistance increases the burden on the mycology laboratory for complete species identification and to determine minimum inhibitory concentration.
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.
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.
<P>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.
</P><P>
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.</P>
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.
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