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Plasmodium falciparum

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https://www.readbyqxmd.com/read/28547798/a-tough-nut-to-crack-intracellular-detection-and-quantification-of-heme-in-malaria-parasites-by-a-genetically-encoded-protein-sensor
#1
Diana Imhof, Amelie Wißbrock
A genetically encoded protein sensor based on HRP2 was used to detect heme in the human malaria parasite Plasmodium falciparum using fluorescence-quenching after heme binding. Protein labels ECFP and EYFP were attached to the termini to allow for a FRET signal as the initial detection parameter before heme binding. The sensor was eventually used to investigate alterations of the labile heme pool during the parasite's life cycle as well as under the influence of the drug chloroquine.
May 26, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28546554/high-throughput-resistance-profiling-of-plasmodium-falciparum-infections-based-on-custom-dual-indexing-and-illumina-next-generation-sequencing-technology
#2
Sidsel Nag, Marlene D Dalgaard, Poul-Erik Kofoed, Johan Ursing, Marina Crespo, Lee O'Brien Andersen, Frank Møller Aarestrup, Ole Lund, Michael Alifrangis
Genetic polymorphisms in P. falciparum can be used to indicate the parasite's susceptibility to antimalarial drugs as well as its geographical origin. Both of these factors are key to monitoring development and spread of antimalarial drug resistance. In this study, we combine multiplex PCR, custom designed dual indexing and Miseq sequencing for high throughput SNP-profiling of 457 malaria infections from Guinea-Bissau, at the cost of 10 USD per sample. By amplifying and sequencing 15 genetic fragments, we cover 20 resistance-conferring SNPs occurring in pfcrt, pfmdr1, pfdhfr, pfdhps, as well as the entire length of pfK13, and the mitochondrial barcode for parasite origin...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546518/safety-immunogenicity-and-cross-species-protection-of-a-plasmid-dna-encoding-plasmodium-falciparum-sera5-polypeptide-microbial-epitopes-and-chemokine-genes-in-mice-and-olive-baboons
#3
Nyamongo Onkoba, Ruth M Mumo, Horace Ochanda, Charles Omwandho, Hastings S Ozwara, Thomas G Egwang
Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines. The present study sought to determine safety, immunogenicity and cross-species efficacy ofPlasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of Bacille-Calmette Guerin (BCG), tetanus toxoid (TT) and a chemokine gene. Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups. The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5+ BCG+ TT alone, or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28545664/a-phenolic-glycoside-from-flacourtia-indica-induces-heme-mediated-oxidative-stress-in-plasmodium-falciparum-and-attenuates-malaria-pathogenesis-in-mice
#4
Shiv Vardan Singh, Ashan Manhas, Suriya P Singh, Sonali Mishra, Nimisha Tiwari, Parmanand Kumar, Karuna Shanker, Kumkum Srivastava, Koneni V Sashidhara, Anirban Pal
BACKGROUND: Flacourtia indica is especially popular among the various communities of many African countries where it is being used traditionally for the treatment of malaria. In our previous report, we have identified some phenolic glycosides from the aerial parts of F. indica as promising antiplasmodial agents under in vitro conditions. PURPOSE: Antimalarial bioprospection of F. indica derived phenolic glycoside in Swiss mice (in vivo) with special emphasis on its mode of action...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28545457/malaria-prevalence-in-asymptomatic-and-symptomatic-children-in-kiwangwa-bagamoyo-district-tanzania
#5
Deborah Sumari, Felista Mwingira, Majige Selemani, Joseph Mugasa, Kefas Mugittu, Paul Gwakisa
BACKGROUND: Malaria prevalence continues to decline across sub-Saharan Africa as a result of various intervention strategies. However, the diseases still poses a public health concern in the region. While symptomatic malaria is recognized and treated, asymptomatic infections become increasingly important for interrupting transmission. A cross-sectional survey was conducted to assess malaria prevalence in symptomatic and asymptomatic children in Kiwangwa ward in Bagamoyo District in Tanzania...
May 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28544379/a-widened-substrate-selectivity-filter-of-eukaryotic-formate-nitrite-transporters-enables-high-level-lactate-conductance
#6
Marie Wiechert, Holger Erler, André Golldack, Eric Beitz
Bacterial formate-nitrite transporters (FNT) regulate the metabolic flow of small weak mono-acids derived from anaerobic mixed-acid fermentation, such as formate, and further transport nitrite, and hydrosulfide. The eukaryotic Plasmodium falciparum FNT is vital for the malaria parasite by its ability to release the larger l-lactate substrate as the metabolic end product of anaerobic glycolysis in symport with protons preventing cytosolic acidification. However, the molecular basis for substrate discrimination by FNTs has remained unclear...
May 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28543853/crystal-structure-of-lipoate-bound-lipoate-ligase-1-lipl1-from-plasmodium-falciparum
#7
Alfredo J Guerra, Gustavo A Afanador, Sean T Prigge
Plasmodium falciparum lipoate protein ligase 1 (PfLipL1) is an ATP-dependent ligase that belongs to the biotin/lipoate A/B protein ligase family (PFAM PF03099). PfLipL1 is the only known canonical lipoate ligase in Pf and functions as a redox switch between two lipoylation routes in the parasite mitochondrion. Here, we report the crystal structure of a deletion construct of PfLipL1 (PfLipL1Δ243-279 ) bound to lipoate, and validate the lipoylation activity of this construct in both an in vitro lipoylation assay and a cell based lipoylation assay...
May 24, 2017: Proteins
https://www.readbyqxmd.com/read/28543724/predicting-binding-modes-of-reversible-peptide-based-inhibitors-of-falcipain-2-consistent-with-structure-activity-relationships
#8
Jorge Enrique Hernández González, Lilian Hernández Alvarez, Pedro Geraldo Pascutti, Pedro Alberto Valiente
Falcipain-2 (FP-2) is a major hemoglobinase of Plasmodium falciparum, considered an important drug target for the development of antimalarials. A previous study reported a novel series of twenty reversible peptide-based inhibitors of FP-2. However, the lack of tridimensional structures of the complexes hinders further optimization strategies to enhance the inhibitory activity of the compounds. Here we report the prediction of the binding modes of the aforementioned inhibitors to FP-2. A computational approach combining previous knowledge on the determinants of binding to the enzyme, docking and post-docking refinement steps, is employed...
May 24, 2017: Proteins
https://www.readbyqxmd.com/read/28543553/enhanced-acquired-antibodies-to-a-chimeric-plasmodium-falciparum-antigen-ub05-09-is-associated-with-protective-immunity-against-malaria
#9
Dinga Jerome Nyhalah, Gamua Stanley Dobgima, Vincent PrydeKehdingha Titanji
It has been shown that covalently linking two antigens could enhance the immunogenicity of the chimeric construct. To prioritise such a chimera for malaria vaccine development it is necessary to demonstrate that naturally acquired antibodies against the chimera are associated with protection from malaria. Here we probe the ability of a chimeric construct of UB05 and UB09 antigens (UB05-09) to better differentiate between acquired immune protection and susceptibility to malaria. In a cross-sectional study, recombinant UB05-09 chimera and the constituent antigens were used to probe for specific antibodies in the plasma from children and adults resident in a malaria endemic zone, using the enzyme-linked immunosorbent assay (ELISA)...
May 24, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28542484/simulating-within-vector-generation-of-the-malaria-parasite-diversity
#10
Lauren M Childs, Olivia F Prosper
Plasmodium falciparum, the most virulent human malaria parasite, undergoes asexual reproduction within the human host, but reproduces sexually within its vector host, the Anopheles mosquito. Consequently, the mosquito stage of the parasite life cycle provides an opportunity to create genetically novel parasites in multiply-infected mosquitoes, potentially increasing parasite population diversity. Despite the important implications for disease transmission and malaria control, a quantitative mapping of how parasite diversity entering a mosquito relates to diversity of the parasite exiting, has not been undertaken...
2017: PloS One
https://www.readbyqxmd.com/read/28542423/plasmid-free-crispr-cas9-genome-editing-in-plasmodium-falciparum-confirms-mutations-conferring-resistance-to-the-dihydroisoquinolone-clinical-candidate-sj733
#11
Emily D Crawford, Jenai Quan, Jeremy A Horst, Daniel Ebert, Wesley Wu, Joseph L DeRisi
Genetic manipulation of the deadly malaria parasite Plasmodium falciparum remains challenging, but the rise of CRISPR/Cas9-based genome editing tools is increasing the feasibility of altering this parasite's genome in order to study its biology. Of particular interest is the investigation of drug targets and drug resistance mechanisms, which have major implications for fighting malaria. We present a new method for introducing drug resistance mutations in P. falciparum without the use of plasmids or the need for cloning homologous recombination templates...
2017: PloS One
https://www.readbyqxmd.com/read/28542247/genetic-polymorphism-of-merozoite-surface-protein-2-msp-2-in-plasmodium-falciparum-isolates-from-pawe-district-north-west-ethiopia
#12
Hussein Mohammed, Moges Kassa, Ashenafi Assefa, Mekonnen Tadesse, Amha Kebede
BACKGROUND: In malaria endemic regions, Plasmodium falciparum infection is characterized by extensive genetic diversity. Describing this diversity provides important information about the local malaria situation. This study was conducted to evaluate the extent of genetic diversity of P. falciparum in Pawe district, North West Ethiopia, using the highly polymorphic merozoite surface protein 2 gene. METHODS: Atotal of 92 isolates from patients with uncomplicated P...
2017: PloS One
https://www.readbyqxmd.com/read/28542223/measuring-changes-in-transmission-of-neglected-tropical-diseases-malaria-and-enteric-pathogens-from-quantitative-antibody-levels
#13
Benjamin F Arnold, Mark J van der Laan, Alan E Hubbard, Cathy Steel, Joseph Kubofcik, Katy L Hamlin, Delynn M Moss, Thomas B Nutman, Jeffrey W Priest, Patrick J Lammie
BACKGROUND: Serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays...
May 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28542123/malaria-surveillance-united-states-2014
#14
Kimberly E Mace, Paul M Arguin
PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission...
May 26, 2017: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
https://www.readbyqxmd.com/read/28540269/species-dependent-clinical-findings-of-malaria-caused-by-various-plasmodia-in-an-endemic-area-of-kerman-province-southeastern-iran
#15
Mehdi Nateghpour, Ali Hosseininasab, Mehrdad Farrokhnia, Foroughieh Dastouri, Katayun Alidoosti, Dadkhoda Sadequi, Asadollah Ahmadi
BACKGROUND: Malaria is a big problem of public health in many tropical countries where socioeconomic development is deficient. Four species of plasmodium are capable of infecting human: P. falciparum, P. malaria, P.vivax, P. ovale. Southeastern corner of Iran, including Sistan and Baluchestan, Hormozgan and the tropical part of Kerman Province, are endemic region of malaria. This study aimed to find out clinical findings in malaria caused by various plasmodium species in moderate transmission area of southern Kerman Province...
April 2017: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/28539634/the-plasmodium-pi-4-k-inhibitor-kdu691-selectively-inhibits-dihydroartemisinin-pretreated-plasmodium-falciparum-ring-stage-parasites
#16
L Dembele, X Ang, M Chavchich, G M C Bonamy, J J Selva, M Yi-Xiu Lim, C Bodenreider, B K S Yeung, F Nosten, B M Russell, M D Edstein, J Straimer, D A Fidock, T T Diagana, P Bifani
Malaria control and elimination are threatened by the emergence and spread of resistance to artemisinin-based combination therapies (ACTs). Experimental evidence suggests that when an artemisinin (ART)-sensitive (K13 wild-type) Plasmodium falciparum strain is exposed to ART derivatives such as dihydroartemisinin (DHA), a small population of the early ring-stage parasites can survive drug treatment by entering cell cycle arrest or dormancy. After drug removal, these parasites can resume growth. Dormancy has been hypothesized to be an adaptive physiological mechanism that has been linked to recrudescence of parasites after monotherapy with ART and, possibly contributes to ART resistance...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28537728/antimalarial-inhibitors-targeting-serine-hydroxymethyltransferase-shmt-with-in-vivo-efficacy-and-analysis-of-their-binding-mode-based-on-x-ray-cocrystal-structures
#17
Geoffrey Schwertz, Matthias C Witschel, Matthias Rottmann, Roger Bonnert, Ubolsree Leartsakulpanich, Penchit Chitnumsub, Aritsara Jaruwat, Wanwipa Ittarat, Anja Schäfer, Raphael A Aponte, Susan A Charman, Karen L White, Abhijit Kundu, Surajit Sadhukhan, Mel Lloyd, Gail M Freiberg, Myron Srikumaran, Marc Siggel, Adrian Zwyssig, Pimchai Chaiyen, François Diederich
Target-based approaches towards new antimalarial treatments are highly valuable to prevent resistance development. We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28537265/a-tetraoxane-based-antimalarial-drug-candidate-that-overcomes-pfk13-c580y-dependent-artemisinin-resistance
#18
Paul M O'Neill, Richard K Amewu, Susan A Charman, Sunil Sabbani, Nina F Gnädig, Judith Straimer, David A Fidock, Emma R Shore, Natalie L Roberts, Michael H-L Wong, W David Hong, Chandrakala Pidathala, Chris Riley, Ben Murphy, Ghaith Aljayyoussi, Francisco Javier Gamo, Laura Sanz, Janneth Rodrigues, Carolina Gonzalez Cortes, Esperanza Herreros, Iñigo Angulo-Barturén, María Belén Jiménez-Díaz, Santiago Ferrer Bazaga, María Santos Martínez-Martínez, Brice Campo, Raman Sharma, Eileen Ryan, David M Shackleford, Simon Campbell, Dennis A Smith, Grennady Wirjanata, Rintis Noviyanti, Ric N Price, Jutta Marfurt, Michael J Palmer, Ian M Copple, Amy E Mercer, Andrea Ruecker, Michael J Delves, Robert E Sinden, Peter Siegl, Jill Davies, Rosemary Rochford, Clemens H M Kocken, Anne-Marie Zeeman, Gemma L Nixon, Giancarlo A Biagini, Stephen A Ward
K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28535801/molecular-markers-of-anti-malarial-drug-resistance-in-central-west-and-east-african-children-with-severe-malaria
#19
Christian N Nguetse, Ayola Akim Adegnika, Tsiri Agbenyega, Bernhards R Ogutu, Sanjeev Krishna, Peter G Kremsner, Thirumalaisamy P Velavan
BACKGROUND: The Plasmodium falciparum multidrug resistance 1 (PfMDR1), P. falciparum Ca(2+)-ATPase (PfATP6) and Kelch-13 propeller domain (PfK13) loci are molecular markers of parasite susceptibility to anti-malarial drugs. Their frequency distributions were determined in the isolates collected from children with severe malaria originating from three African countries. METHODS: Samples from 287 children with severe malaria [(Gabon: n = 114); (Ghana: n = 89); (Kenya: n = 84)] were genotyped for pfmdr1, pfatp6 and pfk13 loci by DNA sequencing and assessing pfmdr1 copy number variation (CNV) by real-time PCR...
May 23, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28535797/within-host-selection-of-drug-resistance-in-a-mouse-model-of-repeated-interrupted-treatment-of-plasmodium-yoelii-infection
#20
Suci Nuralitha, Josephine E Siregar, Din Syafruddin, Andy I M Hoepelman, Sangkot Marzuki
BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone and pyrimethamine in Plasmodium yoelii was examined in such a model. METHODS: Treatment of P. yoelii infected mice, with atovaquone or pyrimethamine, was started at parasitaemia level of 3-5%, interrupted when reduced to less than 0...
May 23, 2017: Malaria Journal
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