39 results on '"Pillai CR"'
Search Results
2. In vitro sensitivity pattern of chloroquine and artemisinin in Plasmodium falciparum
- Author
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Sharma, Supriya, Kaitholia, Kamlesh, Mishra, Neelima, Srivastava, Bina, Pillai, CR, Valecha, Neena, and Anvikar, Anupkumar R
- Published
- 2016
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3. In vitrosensitivity pattern of chloroquine and artemisinin in Plasmodium falciparum
- Author
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Sharma, Supriya, Kaitholia, Kamlesh, Mishra, Neelima, Srivastava, Bina, Pillai, CR, Valecha, Neena, and Anvikar, Anupkumar R
- Abstract
Artemisinin (ART) and its derivatives form the mainstay of antimalarial therapy. Emergence of resistance to them poses a potential threat to future malaria control and elimination on a global level. It is important to know the mechanism of action of drug and development of drug resistance. We put forwards probable correlation between the mode of action of chloroquine (CQ) and ART. Modified trophozoite maturation inhibition assay, WHO Mark III assay and molecular marker study for CQ resistance at K76T codon in Plasmodium falciparumCQ-resistant transporter gene were carried out on cultured P. falciparum. On comparing trophozoite and schizont growth for both CQ-sensitive (MRC-2) and CQ-resistant (RKL-9) culture isolates, it was observed that the clearance of trophozoites and schizonts was similar with both drugs. The experiment supports that CQ interferes with heme detoxification pathway in food vacuoles of parasite, and this may be correlated as one of the plausible mechanisms of ART.
- Published
- 2016
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4. Conserved Plasmodium Protein (PF3D7_0406000) of Unknown Function: In-silico Analysis and Cellular Localization.
- Author
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Pandey I, Quadiri A, Wadi I, Pillai CR, Singh AP, and Das A
- Subjects
- Animals, Antibodies genetics, Humans, Malaria, Falciparum parasitology, Mice, Peptides genetics, Transcriptome genetics, Up-Regulation genetics, Plasmodium falciparum genetics, Protozoan Proteins genetics
- Abstract
In spite of a decrease in malaria cases, the threat of malaria due to Plasmodium falciparum still prevails. The sequencing of Plasmodium falciparum reveals that approximately 60% of the Plasmodium genes code for hypothetical/putative proteins. Here we report an in silico characterization and localization of one such protein. This was encoded by one of the hub genes, in a weighted gene co-expression based systems network, from in-vivo samples of patients suffering from uncomplicated malaria or complicated malaria disease like jaundice and jaundice with renal failure. Interestingly, the protein PF3D7_0406000 (PFD0300w) is classified as a conserved protein of unknown function and shows no identity with any protein from the human host. The transcriptomic data shows up-regulation of transcripts in cases of malaria induced disease complications. PFD0300w peptide antibody based immunolocalization studies using a, gametocyte producing P. falciparum strain RKL-9, shows presence of the protein in the cytoplasm of both asexual and sexual stage parasites., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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5. A novel quinoline-appended chalcone derivative as potential Plasmodium falciparum gametocytocide.
- Author
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Kumar H, Wadi I, Devaraji V, Pillai CR, and Ghosh SK
- Subjects
- Life Cycle Stages drug effects, Ligands, Protein Binding, Protozoan Proteins chemistry, Antimalarials pharmacology, Chalcones pharmacology, Molecular Docking Simulation, Plasmodium falciparum drug effects, Quinolines pharmacology
- Abstract
Background & Objectives: Malaria has remained a global health problem despite the effective control and treatment measures. In the backdrop of drug resistance, developing novel hybrid molecules targeting the sexual stages (gametocytes) of the human malaria parasite Plasmodium falciparum is of great significance. Recently, chalcone- based polyphenols have generated a great interest in the malaria research community worldwide due to their ease of synthesis and significant biological activity. The primary objective of this study was to investigate the interaction of a newly synthesized quinoline-appended chalcone derivative (ADMQ) with gametocyte specific proteins, Pfg 27 and Pfs 25 and explore its in vitro gametocytocidal potential., Methods: The characterization of ligand-protein interactions at the atomistic level was done by a simulation strategy that combines molecular docking and molecular dynamics (MD) simulation in a coherent workflow. The X-ray crystal structure of Pfg 27 was retrieved from protein data bank and Pfs 25 was built using the Iterative Threading ASSembly Refinement (I-TASSER) server. The detailed interaction of both ADMQ and a known gametocytocidal agent, methylene blue (MB) (used as a positive control) with gametocyte proteins Pfg 27 and Pfs 25 was studied with a 50 ns explicit MD simulation. The ligand binding pose in terms of glide score, molecular mechanics-generalized born surface area (MM-GBSA) binding energies, protein-ligand root-mean-square-deviation (RMSD) and secondary structure elements (SSE) changes were analyzed accordingly. The direct effect of ADMQ on structural integrity of P. falciparum gametocytes was also examined using in vitro microscopy., Results: The analogous Glide score and MM-GBSA free energy of binding indicated stable interactions for both ADMQ and MB harboured in the active site of targeted gametocyte proteins, Pfg 27 and Pfs 25, separately. Explicit MD simulation by Desmond software package indicated similar distinguishable conformational changes in the active site of target polypeptide chain due to the specific accommodation of ADMQ molecule. The simulation also manifested comparable mechanistic profile in terms of protein-ligand RMSD and changes in secondary structure elements (SSE). Further, ADMQ treatment was found to adversely affect the structural integrity of gametocytes, which resulted in appearance of vesicles protruding from the gametocytes., Interpretation & Conclusion: The consolidated in silico molecular modeling and in vitro study described herein may give an insight into the interaction patterns of quinoline-chalcone hybrids with critical gametocyte proteins in the mosquito. This study will possibly pave the way for further exploration of similar heterocyclic quinoline-chalcone hybrids to open up new avenues in drug candidate development against P. falciparum gametocytes., Competing Interests: None
- Published
- 2019
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6. Critical examination of approaches exploited to assess the effectiveness of transmission-blocking drugs for malaria.
- Author
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Wadi I, Anvikar AR, Nath M, Pillai CR, Sinha A, and Valecha N
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- Animals, Antimalarials therapeutic use, Gametogenesis drug effects, Humans, Life Cycle Stages drug effects, Malaria parasitology, Molecular Targeted Therapy methods, Parasitic Sensitivity Tests methods, Plasmodium growth & development, Antimalarials pharmacology, Drug Discovery methods, Malaria drug therapy, Malaria transmission, Plasmodium drug effects
- Abstract
In the absence of clinically proven vaccines and emerging resistance to common antimalarials and insecticides, the onus of interrupting the life cycle of Plasmodium falciparum, is upon the transmission-blocking drugs. Current transmission-blocking drug primaquine finds its use restricted because of associated hemolytic toxicity issues in Glucose-6-Phosphate-Dehydrogenase deficient individuals. This article provides an extensive review of the assays used by the investigators to evaluate the transmission-blocking activity of drugs. Furthermore, limitations in existing transmission-blocking assessment approaches/studies are also covered in detail. This review is expected to help in the identification of lacunae in current understanding of transmission-blocking strategies, which are hindering our efforts to develop sustainable and effective transmission-blocking interventions.
- Published
- 2018
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7. Pyrazole-pyrazoline as promising novel antimalarial agents: A mechanistic study.
- Author
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Kumar G, Tanwar O, Kumar J, Akhter M, Sharma S, Pillai CR, Alam MM, and Zama MS
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- Antimalarials chemistry, Antimalarials pharmacology, Chloroquine pharmacology, Hemin antagonists & inhibitors, Plasmodium falciparum drug effects, Pyrazoles chemistry, Sulfonamides chemistry, Benzenesulfonamides, Antimalarials chemical synthesis, Pyrazoles chemical synthesis
- Abstract
A series of pyrazole-pyrazoline substituted with benzenesulfonamide were synthesized and evaluated for their antimalarial activity in vitro and in vivo. The compounds were active against both chloroquine (CQ) sensitive (3D7) and CQ resistant (RKL-9) strains of Plasmodium falciparum. Seven compounds (7e, 7i, 7j, 7l, 7m, 7o and 7p) exhibiting EC
50 less than 2 μM. A mechanistic study of compound 7o revealed that these compound act through the inhibition of β-hematin. The study indicated that these compounds can serve as lead compounds for further development of potent antimalarial drugs., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)- Published
- 2018
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8. Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking.
- Author
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Wadi I, Pillai CR, Anvikar AR, Sinha A, Nath M, and Valecha N
- Subjects
- Humans, India, Inhibitory Concentration 50, Malaria, Falciparum parasitology, Microscopy, Parasitic Sensitivity Tests, Antimalarials pharmacology, Cell Survival drug effects, Methylene Blue pharmacology, Plasmodium falciparum cytology, Plasmodium falciparum drug effects
- Abstract
Background: Malaria remains a global health problem despite availability of effective tools. For malaria elimination, drugs targeting sexual stages of Plasmodium falciparum need to be incorporated in treatment regimen along with schizonticidal drugs to interrupt transmission. Primaquine is recommended as a transmission blocking drug for its effect on mature gametocytes but is not extensively utilized because of associated safety concerns among glucose-6-phosphate dehydrogenase (G6PD) deficient patients. In present work, methylene blue, which is proposed as an alternative to primaquine is investigated for its gametocytocidal activity amongst Indian field isolates. An effort has been made to establish Indian field isolates of P. falciparum as in vitro model for gametocytocidal drugs screening., Methods: Plasmodium falciparum isolates were adapted to in vitro culture and induced to gametocyte production by hypoxanthine and culture was enriched for gametocyte stages using N-acetyl-glucosamine. Gametocytes were incubated with methylene blue for 48 h and stage specific gametocytocidal activity was evaluated by microscopic examination., Results: Plasmodium falciparum field isolates RKL-9 and JDP-8 were able to reproducibly produce gametocytes in high yield and were used to screen gametocytocidal drugs. Methylene blue was found to target gametocytes in a concentration dependent manner by either completely eliminating gametocytes or rendering them morphologically deformed with mean IC
50 (early stages) as 424.1 nM and mean IC50 (late stages) as 106.4 nM. These morphologically altered gametocytes appeared highly degenerated having shrinkage, distortions and membrane deformations., Conclusions: Field isolates that produce gametocytes in high yield in vitro can be identified and used to screen gametocytocidal drugs. These isolates should be used for validation of gametocytocidal hits obtained previously by using lab adapted reference strains. Methylene blue was found to target gametocytes produced from Indian field isolates and is proposed to be used as a gametocytocidal adjunct with artemisinin-based combination therapy. Further exploration of methylene blue in clinical studies amongst Indian population, including G6PD deficient patients, is recommended.- Published
- 2018
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9. In vitro susceptibility of Indian Plasmodium falciparum isolates to different antimalarial drugs & antibiotics.
- Author
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Agarwal P, Anvikar AR, Pillai CR, and Srivastava K
- Subjects
- Artemether, Artemisinins therapeutic use, Atovaquone therapeutic use, Azithromycin therapeutic use, Chloroquine analogs & derivatives, Chloroquine therapeutic use, Doxycycline therapeutic use, Ethanolamines therapeutic use, Fluorenes therapeutic use, Humans, India epidemiology, Lumefantrine, Malaria, Falciparum epidemiology, Malaria, Falciparum parasitology, Mefloquine therapeutic use, Plasmodium falciparum pathogenicity, Quinine therapeutic use, Quinolines therapeutic use, Anti-Bacterial Agents therapeutic use, Antimalarials therapeutic use, Malaria, Falciparum drug therapy, Plasmodium falciparum drug effects
- Abstract
Background & Objectives: : The in vitro assays for susceptibility of Plasmodium falciparum to antimalarial drugs are important tools for monitoring drug resistance. During the present study, efforts were made to establish long-term continuous in vitro culture of Indian field isolates of P. falciparum and to determine their sensitivity to standard antimalarial drugs and antibiotics., Methods: Four (MZR-I, -II, -III and -IV) P. falciparum isolates were obtained from four patients who showed artemisinin-based combination therapy (ACT) from Mizoram, a north-eastern State of India, and characterized for their in vitro susceptibility to chloroquine diphosphate (CQ), quinine hydrochloride dehydrate, mefloquine, piperaquine, artemether, arteether, dihydro-artemisinin (DHA), lumefantrine and atovaquone and antibiotics, azithromycin and doxycycline. These patients showed ACT treatment failure. Two-fold serial dilutions of each drug were tested and the effect was evaluated using the malaria SYBR Green I fluorescence assay. K1 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) reference strains were used as controls., Results: Growth profile of all field isolates was identical to that of reference parasites. The IC50 values of all the drugs were also similar against field isolates and reference parasite strains, except K1, exhibited high IC50 value (275±12.5 nM) of CQ for which it was resistant. All field isolates exhibited higher IC50 values of CQ, quinine hydrochloride dihydrate and DHA compared to reference strains. The resistance index of field isolates with respect to 3D7 ranged between 260.55 and 403.78 to CQ, 39.83 and 46.42 to quinine, and 2.98 and 4.16 to DHA, and with respect to K1 strain ranged between 6.51 and 10.08, 39.26 and 45.75, and 2.65 and 3.71. MZR-I isolate exhibited highest resistance index., Interpretation & Conclusions: As the increase in IC50 and IC90 values of DHA against field isolates of P. falciparum was not significant, the tolerance to DHA-piperaquine (PPQ) combination might be because of PPQ only. Further study is required on more number of such isolates to generate data for a meaningful conclusion., Competing Interests: None.
- Published
- 2017
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10. Effect of efflux pump inhibition on Pseudomonas aeruginosa transcriptome and virulence.
- Author
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Rampioni G, Pillai CR, Longo F, Bondì R, Baldelli V, Messina M, Imperi F, Visca P, and Leoni L
- Subjects
- Bacterial Proteins genetics, Bacterial Proteins metabolism, Gene Expression Profiling, Gene Expression Regulation, Bacterial drug effects, Phenotype, Promoter Regions, Genetic, Pseudomonas aeruginosa pathogenicity, Virulence, Dipeptides pharmacology, Membrane Transport Proteins metabolism, Pseudomonas aeruginosa genetics, Pseudomonas aeruginosa metabolism, Transcriptome
- Abstract
Efflux pumps of the resistance-nodulation-cell-division (RND) family increase antibiotic resistance in many bacterial pathogens, representing candidate targets for the development of antibiotic adjuvants. RND pumps have also been proposed to contribute to bacterial infection, implying that efflux pump inhibitors (EPIs) could also act as anti-virulence drugs. Nevertheless, EPIs are usually investigated only for their properties as antibiotic adjuvants, while their potential anti-virulence activity is seldom taken into account. In this study it is shown that RND efflux pumps contribute to Pseudomonas aeruginosa PAO1 pathogenicity in an insect model of infection, and that the well-characterized EPI Phe-Arg-β-naphthylamide (PAβN) is able to reduce in vivo virulence of the P. aeruginosa PAO1 laboratory strain, as well as of clinical isolates. The production of quorum sensing (QS) molecules and of QS-dependent virulence phenotypes is differentially affected by PAβN, depending on the strain. Transcriptomic and phenotypic analyses showed that the protection exerted by PAβN from P. aeruginosa PAO1 infection in vivo correlates with the down-regulation of key virulence genes (e.g. genes involved in iron and phosphate starvation). Since PAβN impacts P. aeruginosa virulence, anti-virulence properties of EPIs are worthy to be explored, taking into account possible strain-specificity of their activity.
- Published
- 2017
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11. Antimicrobial and antimalarial properties of medicinal plants used by the indigenous tribes of Andaman and Nicobar Islands, India.
- Author
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Chander MP, Pillai CR, Sunish IP, and Vijayachari P
- Subjects
- Anti-Infective Agents isolation & purification, Anti-Infective Agents toxicity, Antimalarials isolation & purification, Antimalarials toxicity, Bacteria drug effects, Disk Diffusion Antimicrobial Tests, Erythrocytes drug effects, Fungi drug effects, Hemolysis, Humans, India, Islands, Phytochemicals isolation & purification, Phytochemicals toxicity, Plant Extracts isolation & purification, Plant Extracts toxicity, Plasmodium falciparum drug effects, Population Groups, Anti-Infective Agents pharmacology, Antimalarials pharmacology, Phytochemicals pharmacology, Plant Extracts pharmacology, Plants, Medicinal chemistry
- Abstract
In this study, methanol extracts of six medicinal plants (Alstonia macrophylla, Claoxylon indicum, Dillenia andamanica, Jasminum syringifolium, Miliusia andamanica and Pedilanthus tithymaloides) traditionally used by Nicobarese tribes of Andaman and Nicobar Islands were studied for antimicrobial and antimalarial activities as well as preliminary photochemical analysis. Plants were collected from Car Nicobar of Andaman and Nicobar Islands and the ethnobotanical data were gathered from traditional healers who inhabit the study area. The methanol extracts were obtained by cold percolation method and the antimicrobial activity was found using agar well diffusion method. Among the plants tested, J. syringifolium, D. andamanica, C. indicum were most active. The antimalarial activity was evaluated against Plasmodium falciparum chloroquine-sensitive MRC-2 isolate. The crude extract of M. andamanica showed excellent antimalarial activity followed by extracts of P. tithymaloides, J. syringifolium and D. andamanica. The chemical injury to erythrocytes was also carried out and it showed that, there were no morphological changes in erythrocytes by the methanol crude extracts. The in vitro antimicrobial and antimalarial activity might be due to the presence of alkaloids, flavonoids, triterpenes, sterols, tannins and saponins in the methanol extracts of tested plants., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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12. In vitro anti-plasmodial activity of some traditionally used medicinal plants against Plasmodium falciparum.
- Author
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Venkatesalu V, Gopalan N, Pillai CR, Singh V, Chandrasekaran M, Senthilkumar A, and Chandramouli N
- Subjects
- Antimalarials isolation & purification, Humans, Inhibitory Concentration 50, Parasitic Sensitivity Tests, Plant Extracts isolation & purification, Antimalarials pharmacology, Plant Extracts pharmacology, Plants, Medicinal chemistry, Plasmodium falciparum drug effects
- Abstract
The anti-plasmodial activity of different solvent extracts of Adhatoda vasica (root), Caesalpinia pulcherrima (leaf), Carica papaya (pulp), Erythroxylum monogynum (leaf), Lantana camara (whole plant), Ocimum sanctum (root) and Phyllanthus niruri (whole plant) were studied against Plasmodium falciparum. Of the 35 extracts tested, seven extracts showed good anti-plasmodial activity. Methanol extract of C. pulcherrima showed the lowest IC50 value (10.96 μg/mL) followed by methanol extract of A. vasica (IC(50)=11.1 μg/mL), chloroform extract of O. sanctum (IC(50)=11.47 μg/mL), methanol extract of E. monogynum (IC(50)=12.23 μg/mL), acetone extract of C. pulcherrima (IC(50)=12.49 μg/mL), methanol extract of O. sanctum and acetone extract of A. vasica (IC(50)=14.04 μg/mL). The results of the present study justify the use of these medicinal plants in traditional practice, and also, a further study on the isolation of anti-plasmodial molecules from their active crude extracts is in progress.
- Published
- 2012
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13. In vitro assessment of drug resistance in Plasmodium falciparum in five States of India.
- Author
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Anvikar AR, Sharma B, Sharma SK, Ghosh SK, Bhatt RM, Kumar A, Mohanty SS, Pillai CR, Dash AP, and Valecha N
- Subjects
- Amodiaquine analogs & derivatives, Amodiaquine pharmacology, Artemisinins pharmacology, Artesunate, Chloroquine pharmacology, Humans, In Vitro Techniques, India, Mefloquine pharmacology, Mutation, Plasmodium falciparum genetics, Biomarkers, Pharmacological, Drug Resistance genetics, Membrane Transport Proteins genetics, Plasmodium falciparum pathogenicity, Protozoan Proteins genetics
- Abstract
Background & Objectives: In vitro assays are an important tool to assess baseline sensitivity and monitor the drug response of Plasmodium falciparum over time and place and, therefore, can provide background information for the development and evaluation of drug policies. This study was aimed at determining the in vitro sensitivity of P. falciparum isolates to antimalarials., Methods: The in vitro activity of 108 P. falciparum isolates obtained from five States of India was evaluated using WHO microtest (Mark III) to chloroquine, monodesethylamodiaquine, dihydroartesunate and mefloquine. Samples were collected from the States of Orissa, Jharkhand, Karnataka, Goa and Chhattisgarh from September 2007 to August 2009. In addition, representative samples from different States of India cryopreserved and culture adapted in the Malaria Parasite Bank of National Institute of Malaria Research, New Delhi, were also evaluated., Results: The proportion of isolates resistant to chloroquine and monodesethylamodiaquine was 44.4 and 25 per cent, respectively. Of the 27 isolates resistant to monodesethylamodiaquine, 16 (59.3%) were cross-resistant to chloroquine. No isolate showed resistance to dihydroartesunate and mefloquine. Isolates from Orissa showed the highest degree of resistance to chloroquine and amodiaquine followed by Jharkhand. Forty two isolates were genotyped for pfcrt T76K chloroquine resistant mutation; mutations were seen in 38 (90.47%) isolates., Interpretation & Conclusions: The Indian P. falciparum isolates showed a high degree of resistance to chloroquine followed by monodesethylamodiaquine. No resistance was recorded to mefloquine and dihydroartesunate.
- Published
- 2012
14. Functional characterization of the quorum sensing regulator RsaL in the plant-beneficial strain Pseudomonas putida WCS358.
- Author
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Rampioni G, Bertani I, Pillai CR, Venturi V, Zennaro E, and Leoni L
- Subjects
- Bacterial Proteins metabolism, DNA Footprinting, DNA, Bacterial metabolism, Electrophoretic Mobility Shift Assay, Plants microbiology, Promoter Regions, Genetic, Protein Binding, Pseudomonas aeruginosa genetics, Pseudomonas aeruginosa physiology, Pseudomonas putida genetics, Siderophores metabolism, Gene Expression Regulation, Bacterial, Pseudomonas putida physiology, Quorum Sensing, Repressor Proteins metabolism
- Abstract
In many bacteria, quorum sensing (QS) systems rely on a signal receptor and a synthase producing N-acyl-homoserine lactone(s) as the signal molecule(s). In some species, the rsaL gene, located between the signal receptor and synthase genes, encodes a repressor limiting signal synthase expression and hence signal molecule production. Here we investigate the molecular mechanism of action of the RsaL protein in the plant growth-promoting rhizobacterium Pseudomonas putida WCS358 (RsaL(WCS)). In P. putida WCS358, RsaL(WCS) displayed a strong repressive effect on the promoter of the QS signal synthase gene, ppuI, while it did not repress the same promoter in Pseudomonas aeruginosa. DNase I protection assays showed that purified RsaL(WCS) specifically binds to ppuI on a DNA region overlapping the predicted σ(70)-binding site, but such protection was observed only at high protein concentrations. Accordingly, electrophoretic mobility shift assays showed that the RsaL(WCS) protein was not able to form stable complexes efficiently with a probe encompassing the ppuI promoter, while it formed stable complexes with the promoter of lasI, the gene orthologous to ppuI in P. aeruginosa. This difference seems to be dictated by the lower dyad symmetry of the RsaL(WCS)-binding sequence on the ppuI promoter relative to that on the lasI promoter. Comparison of the results obtained in vivo and in vitro suggests that RsaL(WCS) needs a molecular interactor/cofactor specific for P. putida WCS358 to repress ppuI transcription. We also demonstrate that RsaL(WCS) regulates siderophore-mediated growth limitation of plant pathogens and biofilm formation, two processes relevant for plant growth-promoting activity.
- Published
- 2012
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15. Anti-plasmodial effects of Azadirachta indica in experimental cerebral malaria: Apoptosis of cerebellar Purkinje cells of mice as a marker.
- Author
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Farahna M, Bedri S, Khalid S, Idris M, Pillai CR, and Khalil EA
- Abstract
Background: Malaria is a major public health problem in the world, but treatment of malaria is becoming more difficult due to increasing drug resistance. Therefore, the need for alternative drugs is acute., Aims: This study investigated the antiplasmodial and protective effect of an ethanolic extract of the leaves from a traditionally used medicinal plant, Azadirachta indica (Neem) in a mouse model of malaria., Materials and Methods: Swiss albino mice were intraperitoneally infected with 10×10(6)Plasmodium berghei ANKA, a rodent malaria parasite. The presence of parasites was checked by microscopic examination of blood samples daily. Ethanolic extracts of Neem at 300, 500 and 1000 mg/kg were administered intraperitoneally daily for five days from the day parasitaemia reach 5% of parasite inoculation. Intraperitoneal chloroquine and artemether were used as standard drug treatment controls. Symptoms of neurological or respiratory disorder, mortality, weight and temperature were recorded. Histological sections of brain were prepared and examined after staining with hematoxylin-eosin and immunohistochemistry for apoptotic cells., Results: All Neem treatment groups displayed parasitaemia that gradually increased during treatment, and showed signs of terminal illness (i.e. hypothermia, ptosis and convulsions) within 2-4 days post-treatment. In contrast, the chloroquine and artemether groups showed no cerebral malaria symptoms and no deaths. Apoptosis in Purkinje cells, cerebral haemorrhage and oedema were found in some of the mice treated with Neem and chloroquine., Conclusions: Azadirachta indica (Neem) extract was not protective against malaria symptoms and signs in this mouse model. However, a difference in the number of apoptotic Purkinje cells between the untreated control group and Neem treatment at 500 mg/kg suggests that Neem may have some neuronal protective effect.
- Published
- 2010
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16. Expression, purification and characterization of allelic variants of MSP-1(42) from Indian Plasmodium falciparum isolates.
- Author
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Lalitha PV, Biswas S, Pillai CR, Seth RK, and Saxena RK
- Subjects
- Alleles, Animals, Base Sequence, Cell Proliferation, Cloning, Molecular, India, Merozoite Surface Protein 1 genetics, Mice, Molecular Sequence Data, Plasmodium falciparum genetics, Plasmodium falciparum isolation & purification, Rabbits, Recombinant Proteins immunology, Sequence Alignment, T-Lymphocytes immunology, Merozoite Surface Protein 1 immunology, Plasmodium falciparum immunology
- Abstract
The C-terminal 19 and 42 kDa fragments of Plasmodium falciparum merozoite surface protein 1 (MSP-1) have shown to be protective in animals against lethal parasite challenge. The MSP-1(19) being highly conserved may lack sufficient number of T-cell epitopes in order to elicit a broader response in genetically diverse populations. The inclusion of additional epitopes from the N-terminal MSP-1(42) has shown to enhance the protective efficacy of MSP-1(19) vaccine. In an attempt to examine the strain specific immunogenicity to MSP-1, we have cloned and expressed three diverse allelic variants of MSP-1(42) from Indian P. falciparum isolates in bacteria. Among three alleles, one was extremely rare and not been found before. These purified and refolded recombinant products were recognized by conformation specific monoclonal antibodies and hyper-immune sera. Immunization of mice and rabbits with the purified proteins generated high titer biologically active polyclonal antibodies supporting further development of this vaccine candidate antigen., ((c) 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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17. Immunogenicity of a recombinant malaria vaccine candidate, domain I+II of AMA-1 ectodomain, from Indian P. falciparum alleles.
- Author
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Lalitha PV, Biswas S, Pillai CR, and Saxena RK
- Subjects
- Adjuvants, Immunologic administration & dosage, Adjuvants, Immunologic pharmacology, Amino Acid Sequence, Animals, Antibodies, Monoclonal immunology, Antibodies, Protozoan blood, Antibodies, Protozoan immunology, Antibody Specificity, Antigens, Protozoan genetics, Cell Proliferation, Cytokines metabolism, DNA, Protozoan chemistry, DNA, Protozoan genetics, Haplotypes, Humans, Immunoglobulin G blood, India, Lymphocytes immunology, Malaria Vaccines genetics, Malaria, Falciparum prevention & control, Membrane Proteins genetics, Mice, Molecular Sequence Data, Plasmodium falciparum genetics, Plasmodium falciparum isolation & purification, Protozoan Proteins genetics, Rabbits, Sequence Alignment, Sequence Analysis, DNA, Spleen immunology, Vaccines, Synthetic genetics, Vaccines, Synthetic immunology, Antigens, Protozoan immunology, Malaria Vaccines immunology, Malaria, Falciparum parasitology, Membrane Proteins immunology, Plasmodium falciparum immunology, Protozoan Proteins immunology
- Abstract
Among the few vaccine candidates under development, apical membrane antigen (AMA-1) of Plasmodium falciparum is one of the most promising erythrocyte stage malaria vaccine candidates under consideration. The overall structure of AMA-1 appears to be conserved as compared to other surface proteins, but there are numerous amino acid substitutions identified among different P. falciparum isolates. Antisera raised against recombinant AMA-1 or naturally acquired human antibodies were strongly inhibitory only towards homologous parasites. In an attempt to examine the strain specificity of antibodies elicited to AMA-1, we have cloned, expressed and purified two allelic variants of domain I+II of AMA-1 ectodomain from Indian P. falciparum isolates in bacteria. One of these is a new haplotype not reported so far and varies in 18 aa positions from the geographically diverse forms 3D7 and 15 from FVO. Refolded proteins were recognized by a conformation specific monoclonal antibody 4G2.dc1 and hyper immune sera. Immunization of mice and rabbits with the purified proteins using CFA/IFA adjuvant generated high titer polyclonal antibodies. Both the alleles induced high levels of IgG1, IgG2a and IgG2b and a low level of IgG3 in mice. Lymphocyte proliferation assays using splenocytes from immunized mice showed significant proliferative responses and cytokines interleukin-2 (IL-2), IL-4, IL-10 and IFN-gamma presence in the culture supernatants. The anti-AMA-1 rabbit antibodies obtained with both the proteins were active in an in vitro parasite growth invasion/inhibition assay. These results suggest that recombinant AMA-1 domain I+II formulated with CFA/IFA adjuvant elicited cellular and humoral responses and is capable of inducing high titer invasion inhibitory antibodies supporting further development of this vaccine candidate.
- Published
- 2008
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18. Genetic diversity of T-helper cell epitopic regions of circumsporozoite protein of Plasmodium falciparum isolates from India.
- Author
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Bhattacharya PR, Bhatia V, and Pillai CR
- Subjects
- Amino Acid Sequence, Animals, Antigenic Variation, Geography, India, Molecular Sequence Data, Plasmodium falciparum immunology, Polymerase Chain Reaction methods, Protozoan Proteins genetics, Sequence Alignment, Sporozoites, T-Lymphocytes, Helper-Inducer immunology, Antigens, Protozoan genetics, DNA, Protozoan analysis, Epitopes, T-Lymphocyte genetics, Genetic Variation, Malaria, Falciparum immunology, Plasmodium falciparum genetics
- Abstract
Genetic variation in the T-helper cell epitopic regions (Th2R and Th3R) of circumsporozoite protein of 135 Plasmodium falciparum isolates collected from different epidemic and endemic regions of India was studied. Variation in the Th2R and Th3R regions was found to exhibit restricted polymorphism and can be grouped. The variations were not regionally biased, as different isolates collected from different regions were found to belong to the same group. The Th2R and Th3R sequences were found to be linked in each isolate. Since the variations are regionally unbiased and restricted, the prototype variant from the groups could be included in a subunit polyvalent vaccine against sporozoites.
- Published
- 2006
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19. Widespread occurrence of the Plasmodium falciparum chloroquine resistance transporter (Pfcrt) gene haplotype SVMNT in P. falciparum malaria in India.
- Author
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Vathsala PG, Pramanik A, Dhanasekaran S, Devi CU, Pillai CR, Subbarao SK, Ghosh SK, Tiwari SN, Sathyanarayan TS, Deshpande PR, Mishra GC, Ranjit MR, Dash AP, Rangarajan PN, and Padmanaban G
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Animals, Drug Resistance genetics, Humans, Membrane Transport Proteins, Plasmodium falciparum drug effects, Protozoan Proteins, Chloroquine pharmacology, Haplotypes, Malaria, Falciparum drug therapy, Membrane Proteins genetics, Plasmodium falciparum genetics
- Abstract
The Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T mutation and haplotype (amino acids 72-76) and the P. falciparum multidrug resistance 1 (Pfmdr1) mutation (N86Y) were analyzed as markers of chloroquine resistance in the DNAs of 73 blood samples from patients with P. falciparum malaria in India. Seventy of the 73 DNAs had the Pfcrt K76T mutation. Of these, 66 had the SVMNT haplotype and four had CVIET, the African/Southeast Asian haplotype. Only 20 of 69 DNAs had the Pfmdr1 N86Y mutation. It is surprising that the Pfcrt haplotype in India is predominantly SVMNT, rather than that seen in Southeast Asia. The widespread prevalence of the Pfcrt K76T mutation is a cause for concern.
- Published
- 2004
20. Molecular analysis of the cytoadherence phenotype of a Plasmodium falciparum field isolate that binds intercellular adhesion molecule-1.
- Author
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Chattopadhyay R, Taneja T, Chakrabarti K, Pillai CR, and Chitnis CE
- Subjects
- Amino Acid Sequence, Animals, CD36 Antigens metabolism, CHO Cells, COS Cells, Cell Line, Chlorocebus aethiops, Cricetinae, DNA, Protozoan chemistry, DNA, Protozoan isolation & purification, Endothelial Cells parasitology, Gene Expression, Genes, Protozoan, Humans, Molecular Sequence Data, Plasmodium falciparum genetics, Plasmodium falciparum pathogenicity, Protein Binding, Protein Structure, Tertiary genetics, Protein Structure, Tertiary physiology, Protozoan Proteins chemistry, Protozoan Proteins genetics, Sequence Alignment, Sequence Analysis, DNA, Cell Adhesion, Intercellular Adhesion Molecule-1 metabolism, Plasmodium falciparum metabolism, Protozoan Proteins metabolism
- Abstract
The ability of Plasmodium falciparum-infected erythrocytes to adhere to endothelial receptors and sequester in diverse host organs is an important pathogenic mechanism. Cytoadherence is mediated by variant surface antigens, which are referred to as PfEMP-1 and are encoded by var genes. The extracellular regions of PfEMP-1 contain multiple conserved cysteine-rich domains that are referred to as Duffy-binding-like (DBL) domains. Here, we analyze the adhesive phenotype of an Indian P. falciparum field isolate, JDP8, which binds ICAM-1 but does not bind CD36. This is a unique cytoadherence phenotype because P. falciparum strains that bind ICAM-1 described thus far usually also bind CD36. Moreover, binding to both receptors is thought to be important for static adhesion under flow. The ICAM-1 binding population of P. falciparum JDP8 adheres to endothelial cells under flow despite poor binding to CD36. We have also identified an expressed var gene, JDP8Icvar, which mediates the ICAM-1 binding phenotype of JDP8. Expression of different regions of JDP8Icvar on the surface of COS-7 cells followed by binding assays demonstrates that the ICAM-1 binding domain maps to the DBL2betaC2 domain of JDP8Icvar. Sequence comparison with two previously identified ICAM-1 binding domains of PfEMP-1, which also map to DBLbetaC2 domains, suggests that diverse P. falciparum isolates use a structurally conserved domain to bind ICAM-1. It thus appears that functional constraints may place limits on the extent of sequence diversity in receptor-binding domains of PfEMP-1.
- Published
- 2004
- Full Text
- View/download PDF
21. Bacterially expressed and refolded receptor binding domain of Plasmodium falciparum EBA-175 elicits invasion inhibitory antibodies.
- Author
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Pandey KC, Singh S, Pattnaik P, Pillai CR, Pillai U, Lynn A, Jain SK, and Chitnis CE
- Subjects
- Animals, Antibodies, Protozoan immunology, Carrier Proteins metabolism, Erythrocytes immunology, Escherichia coli genetics, Escherichia coli metabolism, Host-Parasite Interactions, Humans, Malaria Vaccines administration & dosage, Malaria Vaccines immunology, Malaria, Falciparum immunology, Malaria, Falciparum parasitology, Malaria, Falciparum prevention & control, Protein Conformation, Protein Folding, Protozoan Proteins metabolism, Rabbits, Receptors, Cell Surface chemistry, Receptors, Cell Surface immunology, Recombinant Proteins genetics, Recombinant Proteins immunology, Recombinant Proteins metabolism, Antibodies, Protozoan blood, Antigens, Protozoan, Carrier Proteins chemistry, Carrier Proteins immunology, Erythrocytes parasitology, Plasmodium falciparum pathogenicity, Protozoan Proteins chemistry, Protozoan Proteins immunology, Receptors, Cell Surface metabolism
- Abstract
Malaria parasites make specific receptor-ligand interactions to invade erythrocytes. A 175 kDa Plasmodium falciparum erythrocyte binding antigen (EBA-175) binds sialic acid residues on glycophorin A during invasion of human erythrocytes. The receptor-binding domain of EBA-175 lies in a conserved, amino-terminal, cysteine-rich region, region F2 of EBA-175 (PfF2), that is homologous to the binding domains of other erythrocyte binding proteins such as Plasmodium vivax Duffy binding protein. We have developed methods to produce recombinant PfF2 in its functional form. Recombinant PfF2 was expressed in Escherichia coli, purified from inclusion bodies, renatured by oxidative refolding and purified to homogeneity by ion-exchange and gel filtration chromatography. Refolded PfF2 has been characterized using biochemical and biophysical methods and shown to be pure, homogenous and functional in that it binds human erythrocytes with specificity. Immunization with refolded PfF2 yields high titre antibodies that efficiently inhibit P. falciparum invasion of erythrocytes in vitro. Importantly, antibodies raised against PfF2 block invasion by a P. falciparum field isolate that invades erythrocytes using multiple pathways. These observations support the development of recombinant PfF2 as a vaccine candidate for P. falciparum malaria., (Copyright 2002 Elsevier Science B.V.)
- Published
- 2002
- Full Text
- View/download PDF
22. Modulation of the humoral response to repeat and non-repeat sequences of the circumsporozoite protein of Plasmodium vivax using novel adjuvant and delivery systems.
- Author
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Thomas BE, Manocha M, Haq W, Adak T, Pillai CR, and Rao DN
- Subjects
- Analysis of Variance, Animals, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Immunoglobulin G blood, Malaria, Vivax prevention & control, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred CBA, Microscopy, Electron, Microspheres, Regression Analysis, Spectrophotometry, Statistics, Nonparametric, Vaccines, Subunit immunology, Antigens, Protozoan immunology, Malaria Vaccines immunology, Malaria, Vivax immunology, Plasmodium vivax immunology
- Abstract
In the use of sub-unit vaccines, it is important to identify the protective epitopes and to generate the optimal immune response by using appropriate immuno-modulatory adjuvants and/or delivery systems. The main aim of the present study was to generate an MHC-non-restricted immune response against one promising vaccine candidate, the circumsporozoite protein (CSP) of Plasmodium vivax. Four synthetic peptides were chosen: three repeat-region sequences (AA, DA and ANG) and a putative T-cell epitope extended from a conserved region (region II) containing a hepatocyte-binding region (HBP). The humoral response against each peptide was studied in outbred mice and three strains of inbred mice (with different genetic backgrounds). Delivery of each peptide in microspheres or inclusion of a bio-active casein-fragment analogue as adjuvant with alum/liposome delivery considerably enhanced the humoral response against the peptide (when compared with the response to the peptide delivered in alum alone). The maximal immune response was observed when the peptide was delivered in microspheres, with no booster doses required; the antibodies raised against peptide delivered with adjuvant or in modulatory delivery vehicles had two-to five-fold lower binding affinities. The predominant IgG isotypes elicited using microspheres or adjuvant with alum/liposome delivery were IgG(2a)/IgG(2b) and/or IgG(1). Importantly, conjugation of HBP to the B-cell repeat peptides increased the titres of peptide-specific antibodies, especially of antibodies against the supposedly cryptic HBP. Delivery of a mix of all four peptides in microspheres elicited an intense immune response in outbred mice, indicating that such a delivery system efficiently presents the peptides to the immune effector cells. That antibodies in the anti-peptide sera bound strongly to air-dried sporozoites of P. vivax was confirmed by immunofluorescence. The present results, based on the use of individual peptides or a conjugate or cocktail of the peptides, highlight the utility of the casein-fragment analogue as an adjuvant, when used with alum/liposome delivery, and also demonstrate the potential of microspheres as a single-shot delivery system for sub-unit peptides.
- Published
- 2001
- Full Text
- View/download PDF
23. Investigation of malaria outbreak in Bahraich district, Uttar Pradesh.
- Author
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Dhiman RC, Pillai CR, and Subbarao SK
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, India epidemiology, Male, Population Surveillance, Disease Outbreaks, Malaria, Falciparum epidemiology
- Abstract
Background & Objectives: Based on the reports of 139 fever related deaths in Jarwal primary health centre (PHC) of Bahraich district, Uttar Pradesh (UP) during April to September 1999, a study was undertaken to explore the possibility of outbreak of Plasmodium falciparum malaria in the area and reasons of outbreak., Methods: The study was undertaken during September-October 1999 in Bahraich district, UP. The study included a parasitological and an entomological survey. Blood slides from fever cases were collected and examined following standard procedures for detection of species and stage of parasite. The resting adult mosquitoes were collected from human dwellings and cattle sheds from selected villages. Susceptibility status of Anopheles culicifacies to 4 per cent DDT and 0.05 per cent deltamethrin was determined under laboratory conditions following the WHO procedure. In vitro drug sensitivity of P. falciparum to chloroquine was also estimated., Results: Overall slide positivity rate (SPR) was found to be 33.8 with a preponderance of P. falciparum (88.4%). There was an outbreak of Pf malaria in Jarwal and surrounding areas as well. Foci of P. falciparum malaria were found in Jarwal, Fakharpur and Hazoorpur PHCs around Kaisarganj PHC. In addition, P. falciparum cases, were also reported from Motipur and Tejwapur., Interpretation & Conclusion: Poor surveillance of affected areas resulting in low annual parasite incidence (API), lack of insecticidal spray in the currently affected PHCs as the API was less than 2 and development of resistance in P. falciparum to chloroquine were found as the possible reasons for the outbreak. It is recommended that surveillance be strengthened in all PHCs of Bahraich district to contain further extension of malaria in northeastern UP.
- Published
- 2001
24. In vitro schizontocidal activity of standard antimalarial drugs on chloroquine-sensitive and chloroquine-resistant isolates of Plasmodium falciparum.
- Author
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Sharma P, Pillai CR, and Devi Sharma J
- Subjects
- Animals, Drug Resistance, In Vitro Techniques, Antimalarials pharmacology, Chloroquine pharmacology, Plasmodium falciparum drug effects
- Abstract
The expanding foci of multiple drug resistant malaria and emergence of different strains requires the reassessment of antimalarial activity with various drugs. In vitro response of a chloroquine sensitive and a chloroquine resistant isolate of P. falciparum to a group of 6 quinine derived and 3 artemisinin derived standard drugs has been screened, to evaluate schizontocidal activity of the drugs. In a conventional test system the IC50s were derived from the log dose response curves and evaluated by a rigorous statistical interpretation. Analysis by Tukey's test was significant for the quinine related drugs (Q < or = 0.01) and excludes the statistical significance of artemisinin related drugs in these isolates. The dose-responses of these two isolates vary with quinine derivatives, with some overlap at lower doses for the sensitive isolate than for the resistant one which manifests at higher doses.
- Published
- 2000
25. Role of macrophages in experimental malaria: VII--studies on adoptive transfer of macrophages.
- Author
-
Pillai CR and Devi CU
- Subjects
- Animals, Malaria parasitology, Male, Mice, Adoptive Transfer, Macrophages immunology, Malaria immunology, Malaria prevention & control, Plasmodium berghei immunology
- Abstract
Adoptive transfer of purified macrophages harvested from normal, Plasmodium berghei infected and latent/cured mice and also macrophages exposed to parasites in vitro were carried out to see the role of macrophages in transferring immunity against P. berghei infection. Macrophages obtained from mice having high parasitaemia at a dose of one million cells/animal showed significant increase in survival period (SP) and K values, compared to controls. Macrophages exposed to low parasite density conferred significant K values only. There was a decrease in prepatent period (PP) in the animal which received macrophages from animals cured 7-11 months compared to controls. The adoptive transfer studies with macrophages conditioned in vitro to parasite contributed towards increased protection of host against P. berghei as expressed by K values only. These studies showed that the macrophages harvested from infected mice were capable of acting as immunogen against P. berghei infection.
- Published
- 2000
26. Plasmodium falciparum field isolates commonly use erythrocyte invasion pathways that are independent of sialic acid residues of glycophorin A.
- Author
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Okoyeh JN, Pillai CR, and Chitnis CE
- Subjects
- Animals, Genotype, Humans, Neuraminidase pharmacology, Polymerase Chain Reaction, Trypsin pharmacology, Erythrocytes parasitology, Glycophorins physiology, N-Acetylneuraminic Acid physiology, Plasmodium falciparum physiology
- Abstract
Erythrocyte invasion by malaria parasites is mediated by specific molecular interactions. Sialic acid residues of glycophorin A are used as invasion receptors by Plasmodium falciparum. In vitro invasion studies have demonstrated that some cloned P. falciparum lines can use alternate receptors independent of sialic acid residues of glycophorin A. It is not known if invasion by alternate pathways occurs commonly in the field. In this study, we used in vitro growth assays and erythrocyte invasion assays to determine the invasion phenotypes of 15 P. falciparum field isolates. Of the 15 field isolates tested, 5 multiply in both neuraminidase and trypsin-treated erythrocytes, 3 multiply in neuraminidase-treated but not trypsin-treated erythrocytes, and 4 multiply in trypsin-treated but not neuraminidase-treated erythrocytes; 12 of the 15 field isolates tested use alternate invasion pathways that are not dependent on sialic acid residues of glycophorin A. Alternate invasion pathways are thus commonly used by P. falciparum field isolates. Typing based on two polymorphic markers, MSP-1 and MSP-2, and two microsatellite markers suggests that only 1 of the 15 field isolates tested contains multiple parasite genotypes. Individual P. falciparum lines can thus use multiple invasion pathways in the field. These observations have important implications for malaria vaccine development efforts based on EBA-175, the P. falciparum protein that binds sialic acid residues of glycophorin A during invasion. It may be necessary to target parasite ligands responsible for the alternate invasion pathways in addition to EBA-175 to effectively block erythrocyte invasion by P. falciparum.
- Published
- 1999
- Full Text
- View/download PDF
27. Strong association, but incomplete correlation, between chloroquine resistance and allelic variation in the pfmdr-1 gene of Plasmodium falciparum isolates from India.
- Author
-
Bhattacharya PR and Pillai CR
- Subjects
- Alleles, Animals, India, Insecticide Resistance genetics, Plasmodium falciparum genetics, Point Mutation, ATP-Binding Cassette Transporters, Antimalarials pharmacology, Chloroquine pharmacology, Plasmodium falciparum drug effects, Protozoan Proteins genetics
- Abstract
The increasing prevalence of chloroquine-resistant Plasmodium falciparum has complicated the control of falciparum malaria. It has been suggested that point mutations at nucleotide positions 754, 1049, 3598, 3622 and 4234 in the parasite's pfmdr-1 gene are associated with such resistance, although this is a matter of controversy. Eighteen chloroquine-sensitive and 22 resistant isolates of P. falciparum from India were investigated, to examine the role of the pfmdr-1 gene in the resistance, and to determine whether any of the point mutations could be used as a marker for the rapid identification of the chloroquine-resistant strains. As this investigation failed to reveal an explicit association between allelic variation in the pfmdr-1 gene and chloroquine resistance, the use of point mutations to identify the resistant strains does not appear feasible.
- Published
- 1999
- Full Text
- View/download PDF
28. Role of macrophages in experimental malaria: VI--Effect of Freund's complete adjuvant in Plasmodium berghei infected mice.
- Author
-
Pillai CR and Usha Devi C
- Subjects
- Animals, Humans, Malaria immunology, Malaria parasitology, Male, Mice, Freund's Adjuvant, Macrophages immunology, Malaria prevention & control, Plasmodium berghei immunology
- Abstract
Freund's complete adjuvant (FCA) treated group of mice when challenged with lethal Plasmodium berghei showed increased survival value; survival period (SP) and median survival day (MSD) compared to their respective control groups. K values were affected and mean parasitaemia during infection period was lower than that of control. In general survival rate after 35 days of infection was 10.5% in FCA recipients. The survival rate in a particular group of animals which received 0.2 ml FCA 3 days before challenge was 22.7%. FCA was found to contribute to increased survival of the host against P. berghei infection. The study indicates that adjuvants, like FCA induce protective immunity and future studies should include non-specific immunization against human malaria.
- Published
- 1999
29. Role of macrophages in experimental malaria: V--Effect of ethyl palmitate on macrophages in Plasmodium berghei infected mice.
- Author
-
Pillai CR and Devi CU
- Subjects
- Animals, Malaria parasitology, Male, Mice, Survival Analysis, Cytotoxins pharmacology, Disease Models, Animal, Macrophages drug effects, Macrophages immunology, Malaria drug therapy, Malaria immunology, Palmitic Acids pharmacology, Plasmodium berghei
- Abstract
Ethyl palmitate (EP) was used as a macrophage cytotoxin. The response of P. berghei after exposing the macrophage to EP was opposite to what was seen with other agents like Silica, Antimacrophage serum and Freund's complete adjuvant. EP at dose of 5 mg and above decreased the survival period (SP), median survival day (MSD) and parasite density 24 hrs. before death (K values). Prepatent period (PP) was lower at doses 10 mg and 20 mg per day for 5 days before challenge compared to their corresponding controls. EP at a dose of 5 mg and above was found to be toxic to host, mice. EP in dosage of 3 mg per mouse administered 48 hrs. before challenge resulted in an increase in the mean survival period, survival rate (30%) and decrease in the mean parasitaemia per day when compared with the corresponding control. The interfering agents affected differently both the host and/or parasite. A proper modulation of the macrophage during the course of infection may help the host in surviving this lethal infection.
- Published
- 1997
30. Role of macrophages in experimental malaria: IV--Bioassay of silica in immunity against Plasmodium berghei infection.
- Author
-
Pillai CR, Devi CU, Choudhury DS, and Singh NN
- Subjects
- Animals, Biological Assay, Malaria metabolism, Male, Mice, Immunity physiology, Malaria immunology, Plasmodium berghei, Silicon Dioxide analysis
- Abstract
Silica treated mice when challenged with Plasmodium berghei showed increase in duration of prepatent(PP) and survival period (SP) and median survival day(MSD) as compared with controls. Daily parasite density curve during the course of infection was similar to control. Response to the parasite challenge, however, was dependent on the dose of silica. No increase in SP at 0.7 mg and in PP at 35 mg (cumulative doses) dose was observed. A dose upto 5 mg per mouse before challenge resulted in protection of the animal. No mortality was recorded in mice which received silica alone (35 mg; 5 mg/day x 7 days). Death due to lethal P.berghei infection could be delayed or prevented by altering/reducing the functional activities of macrophages during the course of infection.
- Published
- 1997
31. High prevalence of chloroquine resistant Plasmodium falciparum infection in Rajasthan epidemic.
- Author
-
Sharma YD, Biswas S, Pillai CR, Ansari MA, Adak T, and Devi CU
- Subjects
- Animals, Antibodies, Protozoan analysis, Drug Resistance, Microbial, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin G analysis, Immunoglobulin M analysis, India epidemiology, Malaria, Falciparum mortality, Mefloquine pharmacology, Microbial Sensitivity Tests, Plasmodium falciparum immunology, Pyrimethamine pharmacology, Quinine pharmacology, Seroepidemiologic Studies, Sulfadoxine pharmacology, Tumor Necrosis Factor-alpha analysis, Antimalarials therapeutic use, Chloroquine therapeutic use, Disease Outbreaks, Malaria, Falciparum drug therapy, Malaria, Falciparum epidemiology, Plasmodium falciparum drug effects
- Abstract
Plasmodium falciparum is the main killer among all human malaria parasites. In 1994, there was a falciparum malaria epidemic in Rajasthan, India, with many deaths. We have investigated active falciparum malaria cases from this epidemic and found that most of the parasite isolates (95%) were resistant to chloroquine. Nevertheless, all the tested isolates from the epidemic, were sensitive to mefloquine and quinine and ninety percent were also susceptible to sulfadoxine/pyrimethamine. Most individuals had moderate levels of TNF-alpha (20-220 pg/ml) and anti-parasite IgM antibodies compared to IgG levels which were relatively lower. In conclusion, the high transmission rate of the chloroquine resistant P. falciparum parasite could be the probable cause of the disease epidemic in Rajasthan. The timely drug sensitivity test and availability of appropriate antimalarial drugs are, therefore, warranted.
- Published
- 1996
- Full Text
- View/download PDF
32. Cerebral malaria.
- Author
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Sharma YD, Kant R, Pillai CR, Ansari MA, and Fillai U
- Subjects
- Animals, Disease Outbreaks, Drug Resistance genetics, Humans, India epidemiology, Malaria, Cerebral drug therapy, Malaria, Cerebral epidemiology, Plasmodium falciparum genetics, Chloroquine therapeutic use, Malaria, Cerebral parasitology, Plasmodium falciparum drug effects
- Published
- 1995
- Full Text
- View/download PDF
33. Role of macrophages in experimental malaria: I. Development of immunobioassay indicators.
- Author
-
Pillai CR and Singh NN
- Subjects
- Animals, Biological Assay, Host-Parasite Interactions, Malaria parasitology, Male, Mice, Plasmodium berghei immunology, Macrophages immunology, Malaria immunology, Plasmodium berghei growth & development
- Abstract
The role of macrophages in immunogenic mechanisms of malaria was studied. The first part of the study aimed at development of indicators for assessing immunobioassay. Accordingly, data on the natural course of lethal Plasmodium berghei infection in mice were collected, and baseline estimates of a set of indicators were made. The indicators along with their estimated means are: prepatent period (PP), 2.57 +/- 0.06 days; survival period (SP), 17.63 +/- 0.29 days; median survival day (MSD), 17.20 days; and parasite density 24 h before death (K), 3582.6 infected RBC/10(4)RBCs. The probable role of immunogenic mechanisms judged indirectly by course of parasitaemia in different phases is discussed.
- Published
- 1993
34. Vaccine against malaria in rodents--a preliminary communication.
- Author
-
Hussian QZ, Pasha ST, Ravindran B, Sethi P, Devi U, Malik IJ, Pillai CR, and Satija NK
- Subjects
- Animals, Antigens, Kupffer Cells transplantation, Liver immunology, Plasmodium berghei immunology, Rats, Transplantation, Homologous, Malaria prevention & control, Vaccination, Vaccines
- Published
- 1976
35. Trypsin-sensitive plasmodia in the liver of post-infection rats and rhesus monkeys.
- Author
-
Hussain QZ, Pillai CR, Ravindran B, and Kaushik N
- Subjects
- Animals, Macaca mulatta, Male, Plasmodium berghei drug effects, Rats, Rats, Inbred Strains, Erythrocytes parasitology, Kupffer Cells parasitology, Malaria parasitology, Plasmodium drug effects, Trypsin pharmacology
- Abstract
Kupffer cells from the liver and erythrocytes from peripheral blood were collected at the post-patent period from albino rats infected earlier with Plasmodium berghei and rhesus monkeys infected earlier with P. cynomolgi var. bastianelli or P. knowlesi. The cells were subinoculated into individual normal recipients. These recipients subsequently showed parasitaemia in their circulation. The parasites present in Kupffer cell preparations were found to be sensitive to trypsin treatment, while those in erythrocytes were found to be resistant to trypsin treatment. This differential sensitivity of parasites to trypsin was observed in all the three species of plasmodia studied so far.
- Published
- 1986
36. Effect of chloroquine and some other antimalarials on the immune mechanism in experimental animals.
- Author
-
Bhattacharya SK, Pillai CR, Mathur M, and Sen P
- Subjects
- Adrenal Glands metabolism, Animals, Antibody Formation drug effects, Ascorbic Acid metabolism, Female, Hypersensitivity, Delayed immunology, Immunity, Cellular drug effects, Leukocyte Count, Male, Mice, Passive Cutaneous Anaphylaxis drug effects, T-Lymphocytes drug effects, Antimalarials pharmacology, Chloroquine pharmacology, Immunity drug effects
- Abstract
The effects of chloroquine and some other antimalarials on the immune responses in experimental animals have been examined. Chloroquine and quinine caused significant decrease of serum anti-SRBC haemagglutination titre. Chloroquine lowered the serum IgM level and also reduced plaque-forming cells in the spleen of mice. The delayed-type hypersensitivity responses to SRBC and the passive cutaneous anaphylaxis were also diminished in rats treated with chloroquine. Thus, the immunosuppressant activity of chloroquine may explain its efficacy in various types of immune disorders.
- Published
- 1984
- Full Text
- View/download PDF
37. Immunoprophylaxis against Kala-Azar. II-Experimental L. donovani infection in Hissar strain albino mice & comparison between mouse adopted and hamster maintained strains.
- Author
-
Jalees S, Jalil S, Pillai CR, Hussain QZ, and Topa PK
- Subjects
- Animals, Bone Marrow parasitology, Cricetinae, Culture Techniques, Immunity, Cellular, Leishmania pathogenicity, Liver parasitology, Mice, Mice, Inbred Strains, Spleen parasitology, Leishmaniasis, Visceral immunology
- Published
- 1982
38. Leucocyte migration inhibition test in human Plasmodium vivax malaria.
- Author
-
Ravindran B, Sharma BK, Pillai CR, and Hussain QZ
- Subjects
- Animals, Antibodies immunology, Humans, Macaca mulatta, Male, Plasmodium falciparum, Cell Migration Inhibition, Leukocytes immunology, Malaria immunology, Plasmodium vivax immunology
- Abstract
Specific antigen-induced T-lymphocyte response in human P. vivax malaria has been studied by a leucocyte migration inhibition test. The test was performed in four groups: (1) American/European controls; (2) Indians with acute P. vivax malaria; (3) immune Indians with no clinical attacks of malaria for 5 years; and (4) Indians with chronic infection. Group 3 showed significantly high inhibition as compared to group 1 (P less than 0.001) and group 2 (P less than 0.01). There was however no significant difference between the 'immune' and 'chronic' groups. Indirect haemagglutinating antibodies were also monitored in the test sera and there was an inverse correlation (r = -0.613; P less than 0.01) between IHA antibodies in serum and percentage leucocyte migration inhibition.
- Published
- 1983
39. Vaccine against simian malaria (P. cynomolgi)--a preliminary communication.
- Author
-
Hussain QZ, Pasha ST, Ravindran B, Malik IJ, Sethi P, Pillai CR, Devi U, and Satija NK
- Subjects
- Animals, Antigens, Blood Cells immunology, Cell Membrane immunology, Haplorhini, Macaca mulatta, Malaria prevention & control, Vaccination, Vaccines
- Published
- 1976
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