Department of Biological Sciences
Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1922
Browse
4 results
Search Results
Item Plasmodium Iron-Sulfur [Fe-S] cluster assembly protein Dre2 as a plausible target of Artemisinin: Mechanistic insights derived in a prokaryotic heterologous system(Elsevier, 2023-06) Garg, Shilpi; Saxena, VishalIron-sulfur (Fe-S) cluster containing proteins have been assigned roles in various essential cellular processes, such as regulation of gene expression, electron transfer, sensing of oxygen and balancing free radical chemistry. However, their role as the drug target remains sparse. Recently the screening of protein alkylation targets for artemisinin in Plasmodium falciparum led to identification of Dre2, a protein involved in redox mechanism for the cytoplasmic Fe-S cluster assembly in different organisms. In the present study, to further explore the interaction between artemisinin and Dre2, we have expressed the Dre2 protein of both P. falciparum and P. vivax in E. coli. The opaque brown colour of the IPTG induced recombinant Plasmodium Dre2 bacterial pellet, suggested iron accumulation as confirmed by the ICP-OES analysis. In addition, overexpression of rPvDre2 in E. coli reduced its viability, growth and increased the ROS levels of bacterial cells, which in turn led to an increase in expression of stress response genes of E. coli such as recA, soxS, mazF. Moreover, the overexpression of rDre2 induced cell death could be rescued by treatment with Artemisinin derivatives suggesting their interaction. The interaction between DHA and PfDre2 was later demonstrated by CETSA and microscale thermophoresis. Overall, this study suggests that Dre2 is the probable target of Artemisinin and the antimalarial activity of DHA/Artemether could also be due to yet unidentified molecular mechanism altering the Dre2 activity in addition to inducing DNA and protein damage.Item Awareness on critical prevention practices to combat the drug resistance in Plasmodium falciparum and Plasmodium vivax malaria from Rajasthan, India(IJMR, 2020) Garg, ShilpiThe ability of the Plasmodium parasites to develop resistance to commonly used antimalarial is the biggest challenge for malaria elimination. This threat is being accelerated by the systematic misuse or overuse of antimalarial, as well as inadequate infection prevention and control. Most disease control strategies require active community participation, which in turn depends on an individual’s knowledge and alertness to the disease. This study was undertaken to understand the awareness of the local public, predominantly rural, regarding the use of antimalarial, current status of drug resistance and critical prevention practices or alternatives used to combat malaria in and around Jhunjhunu, Rajasthan. A questionnaire-based cross-sectional study was designed and data was collected using an observational checklist. On the whole, our data shows that while nearly three fourth of the respondents were aware of the mosquito bite, only 10% knew about the parasite Plasmodium. About one-tenth of the people were aware of Chloroquine as well as drug resistance. Further, to fill the knowledge gaps of the target audiences, malaria control strategies were personalized as an effort to strengthen existing malaria prevention approaches and proper usage of drug regimens to eliminate malaria.Item New Insight into Isoprenoids Biosynthesis Process and Future Prospects for Drug Designing in Plasmodium(Frontiers, 2016-09-13) Garg, Shilpi; Saxena, VishalThe MEP (Methyl Erythritol Phosphate) isoprenoids biosynthesis pathway is an attractive drug target to combat malaria, due to its uniqueness and indispensability for the parasite. It is functional in the apicoplast of Plasmodium and its products get transported to the cytoplasm, where they participate in glycoprotein synthesis, electron transport chain, tRNA modification and several other biological processes. Several compounds have been tested against the enzymes involved in this pathway and amongst them Fosmidomycin, targeted against IspC (DXP reductoisomerase) enzyme and MMV008138 targeted against IspD enzyme have shown good anti-malarial activity in parasite cultures. Fosmidomycin is now-a-days prescribed clinically, however, less absorption, shorter half-life, and toxicity at higher doses, limits its use as an anti-malarial. The potential of other enzymes of the pathway as candidate drug targets has also been determined. This review details the various drug molecules tested against these targets with special emphasis to Plasmodium. We corroborate that MEP pathway functional within the apicoplast of Plasmodium is a major drug target, especially during erythrocytic stages. However, the major bottlenecks, bioavailability and toxicity of the new molecules needs to be addressed, before considering any new molecule as a potent antimalarial.Item Recent Advances in the [Fe–S] Cluster Biogenesis (SUF) Pathway Functional in the Apicoplast of Plasmodium(Elsiever, 2018-07-28) Garg, Shilpi; Saxena, VishalIron–sulphur [Fe–S] clusters are one of the most ancient and ubiquitous cofactors required for a wide variety of proteins active in processes such as electron transport, enzyme catalysis, and gene regulation. In the malaria parasite, Plasmodium, the SUF pathway (Fe–S cluster biosynthesis) is essential for the maintenance of the parasite during the erythrocytic and sexual stages. In Plasmodium, the SUF pathway provides clusters to the enzymes functional in the apicoplast and participating in major metabolic pathways such as fatty acid biosynthesis, isoprenoids biosynthesis, tRNA modifications, etc. The [Fe–S] cluster biogenesis in Plasmodium is similar to the one operational in the bacterial system and can be a putative drug target.