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https://www.readbyqxmd.com/read/28634346/generating-conditional-gene-knockouts-in-plasmodium-a-toolkit-to-produce-stable-dicre-recombinase-expressing-parasite-lines-using-crispr-cas9
#1
Ellen Knuepfer, Marta Napiorkowska, Christiaan van Ooij, Anthony A Holder
Successful establishment of CRISPR/Cas9 genome editing technology in Plasmodium spp. has provided a powerful tool to transform Plasmodium falciparum into a genetically more tractable organism. Conditional gene regulation approaches are required to study the function of gene products critical for growth and erythrocyte invasion of blood stage parasites. Here we employ CRISPR/Cas9 to facilitate use of the dimerisable Cre-recombinase (DiCre) that is frequently used to mediate the excision and loss of loxP-flanked DNA sequences in a rapamycin controlled manner...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634183/syk-inhibitors-interfere-with-erythrocyte-membrane-modification-during-p-falciparum-growth-and-suppress-parasite-egress
#2
Antonella Pantaleo, Kristina R Kesely, Maria Carmina Pau, Ioannis Tsamesidis, Evelin Schwarzer, Oleksii A Skorokhod, Huynh D Chien, Marta Ponzi, Lucia Bertuccini, Philip S Low, Francesco M Turrini
Band 3 (a.k.a. the anion exchanger, SLCA1, AE1) constitutes the major attachment site of the spectrin-based cytoskeleton to the erythrocyte's lipid bilayer and thereby contributes critically to the stability of the red cell membrane. During the intra-erythrocytic stage of Plasmodium falciparum's life cycle, band 3 becomes tyrosine phosphorylated in response to oxidative stress, leading to a decrease in its affinity for the spectrin/actin cytoskeleton and causing global membrane destabilization. Because this membrane weakening is hypothesized to facilitate parasite egress and the consequent dissemination of released merozoites throughout the bloodstream, we decided to explore which tyrosine kinase inhibitors might block the kinase-induced membrane destabilization...
June 20, 2017: Blood
https://www.readbyqxmd.com/read/28634105/genetic-diversity-in-the-c-terminus-of-merozoite-surface-protein-1-among-plasmodium-knowlesi-isolates-from-selangor-and-sabah-borneo-malaysia
#3
Nan Jiun Yap, Xiang Ting Goh, Anson V Koehler, Timothy William, Tsin Wen Yeo, Indra Vythilingam, Robin B Gasser, Yvonne A L Lim
Plasmodium knowlesi, a malaria parasite of macaques, has emerged as an important parasite of humans. Despite the significance of P. knowlesi malaria in parts of Southeast Asia, very little is known about the genetic variation in this parasite. Our aim here was to explore sequence variation in a molecule called the 42kDa merozoite surface protein-1 (MSP-1), which is found on the surface of blood stages of Plasmodium spp. and plays a key role in erythrocyte invasion. Several studies of P. falciparum have reported that the C-terminus (a 42kDa fragment) of merozoite surface protein-1 (MSP-142; consisting of MSP-119 and MSP-133) is a potential candidate for a malaria vaccine...
June 17, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28633997/nicotinamide-inhibits-the-growth-of-p-falciparum-and-enhances-the-antimalarial-effect-of-artemisinin-chloroquine-and-pyrimethamine
#4
Sergey O Tcherniuk, Olga Chesnokova, Irina V Oleinikov, Andrew V Oleinikov
Nicotinamide (vitamin B3) - is a water soluble amide derivative of nicotinic acid, which has been used at high doses for a variety of therapeutic applications. However, its antimalarial effect has not been intensively explored. In this work we analysed the effect of nicotinamide alone and in combination with artemisinin, chloroquine andpyrimethamine on the growth of blood stages of P. falciparum. Our results demonstrate that nicotinamide effectively inhibits the growth of blood stage parasites with IC50 of 6...
June 17, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28633672/influence-of-the-number-and-timing-of-malaria-episodes-during-pregnancy-on-prematurity-and-small-for-gestational-age-in-an-area-of-low-transmission
#5
Kerryn A Moore, Julie A Simpson, Jacher Wiladphaingern, Aung Myat Min, Mupawjay Pimanpanarak, Moo Kho Paw, Jathee Raksuansak, Sasithon Pukrittayakamee, Freya J I Fowkes, Nicholas J White, François Nosten, Rose McGready
BACKGROUND: Most evidence on the association between malaria in pregnancy and adverse pregnancy outcomes focuses on falciparum malaria detected at birth. We assessed the association between the number and timing of falciparum and vivax malaria episodes during pregnancy on small-for-gestational-age (SGA) and preterm birth. METHODS: We analysed observational data collected from antenatal clinics on the Thailand-Myanmar border (1986-2015). We assessed the effects of the total number of malaria episodes in pregnancy on SGA and the effects of malaria in pregnancy on SGA, very preterm birth, and late preterm birth, by the gestational age at malaria detection and treatment using logistic regression models with time-dependent malaria variables (monthly intervals)...
June 21, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28630943/parasites-lacking-the-micronemal-protein-mic2-are-deficient-in-surface-attachment-and-host-cell-egress-but-remain-virulent-in-vivo
#6
Simon Gras, Allison Jackson, Stuart Woods, Gurman Pall, Jamie Whitelaw, Jacqueline M Leung, Gary E Ward, Craig W Roberts, Markus Meissner
Background: Micronemal proteins of the thrombospondin-related anonymous protein (TRAP) family are believed to play essential roles during gliding motility and host cell invasion by apicomplexan parasites, and currently represent major vaccine candidates against Plasmodium falciparum, the causative agent of malaria. However, recent evidence suggests that they play multiple and different roles than previously assumed. Here, we analyse a null mutant for MIC2, the TRAP homolog in Toxoplasma gondii. Methods: We performed a careful analysis of parasite motility in a 3D-environment, attachment under shear stress conditions, host cell invasion and in vivo virulence...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28630631/urinalysis-and-clinical-correlations-in-patients-with-p-vivax-or-p-falciparum-malaria-from-colombia
#7
Alberto Tobón-Castaño, Sebastián Barrera Escobar, Cecilia Giraldo Castro
BACKGROUND: Urinalysis is a poorly reviewed diagnostic tool in malaria patients; its application can show the presence of severe malaria. METHODS: Urinalysis was performed in a total of 620 patients diagnosed with malaria by thick blood smear; complications were classified according to WHO major criteria for severity and minor criteria according to the Colombian malaria guideline. RESULTS: Severe or moderate clinical complications were diagnosed in 31...
2017: Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28630585/identification-of-the-plasmodium-species-in-clinical-samples-from-children-residing-in-five-epidemiological-strata-of-malaria-in-cameroon
#8
Tebit Emmanuel Kwenti, Tayong Dizzle Bita Kwenti, Longdoh Anna Njunda, Andreas Latz, Kukwah Anthony Tufon, Theresa Nkuo-Akenji
BACKGROUND: Malaria in Cameroon was previously known to be caused solely by Plasmodium falciparum but today, evidence points to other Plasmodium species including P. vivax, P. ovale and P. malariae. The purpose of this study was to identify the Plasmodium species in clinical samples from children residing in five epidemiological strata of malaria in Cameroon, so as to advise control policies. METHODS: One thousand six hundred nine febrile children (≤15 years) were recruited from five epidemiological strata of malaria including the Sudano-sahelian (SS) strata, the High inland plateau (HIP) strata, the South Cameroonian Equatorial forest (SCEF) strata, the High western plateau (HWP) strata and the Coastal (C) strata...
2017: Tropical Medicine and Health
https://www.readbyqxmd.com/read/28628279/acyclic-nucleoside-phosphonates-containing-9-deazahypoxanthine-and-a-5-membered-heterocycle-as-selective-inhibitors-of-plasmodial-6-oxopurine-phosphoribosyltransferases
#9
Martin Maxmilian Kaiser, Ondřej Baszczyňski, Dana Hocková, Lenka Poštová-Slavětínská, Martin Dračínský, Dianne T Keough, Luke W Guddat, Zlatko Janeba
Acyclic nucleoside phosphonates (ANPs) are an important class of therapeutic drugs that act as antiviral agents by inhibiting viral DNA polymerases and reverse transcriptases. ANPs containing a 6-oxopurine instead of 6-aminopurine or pyrimidine bases are inhibitors of the purine salvage enzyme, hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase (HG[X]PRT). Such compounds, and their prodrugs, are able to arrest the growth of Plasmodium falciparum (Pf) in cell culture. A new series of ANPs has been synthesized and tested as inhibitors of human HGPRT, PfHGXPRT and Plasmodium vivax (Pv) HGPRT...
June 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28627360/the-plasmodium-falciparum-exported-protein-pf3d7_0402000-binds-to-erythrocyte-ankyrin-and-band-4-1
#10
Bikash Shakya, Wesley D Penn, Ernesto S Nakayasu, Douglas J LaCount
Plasmodium falciparum extensively modifies the infected red blood cell (RBC), resulting in changes in deformability, shape and surface properties. These alterations suggest that the RBC cytoskeleton is a major target for modification during infection. However, the molecular mechanisms leading to these changes are largely unknown. To begin to address this question, we screened for exported P. falciparum proteins that bound to the erythrocyte cytoskeleton proteins ankyrin 1 (ANK1) and band 4.1 (4.1R), which form critical interactions with other cytoskeletal proteins that contribute to the deformability and stability of RBCs...
June 13, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28626547/structure-guided-optimization-of-quinoline-inhibitors-of-plasmodium-n-myristoyltransferase
#11
Victor Goncalves, James A Brannigan, Alice Laporte, Andrew S Bell, Shirley M Roberts, Anthony J Wilkinson, Robin J Leatherbarrow, Edward W Tate
The parasite Plasmodium vivax is the most widely distributed cause of recurring malaria. N-Myristoyltransferase (NMT), an enzyme that catalyses the covalent attachment of myristate to the N-terminal glycine of substrate proteins, has been described as a potential target for the treatment of this disease. Herein, we report the synthesis and the structure-guided optimization of a series of quinolines with balanced activity against both Plasmodium vivax and Plasmodium falciparum N-myristoyltransferase (NMT).
January 1, 2017: MedChemComm
https://www.readbyqxmd.com/read/28626211/once-malaria-is-eliminated-more-attention-should-be-paid-to-imported-malaria-data-from-five-years-of-surveillance-in-the-city-of-yiwu-in-eastern-china
#12
Xuanjun Dong, Jie Yang, Lianqin Lou, Liebo Zhu, Xiayan Feng, Linong Yao
This study reviewed and analyzed data on malaria cases in Yiwu from 2012 to 2016 via a webbased system for managing and reporting information on infectious diseases. A total of 161 cases were diagnosed (77.02% due to Plasmodium falciparum, 18.01% due to P. vivax, 4.35% due to P. ovale, and 0.62% due to P. malariae). One case was imported from Yunnan Province in China and the others were imported from overseas. The ratio of male to female patients was 7.47:1. The average age was 36.34 years (SD: 9.63). Most cases (87...
June 18, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28623926/perennial-transmission-of-malaria-in-the-low-altitude-areas-of-baringo-county-kenya
#13
Collince J Omondi, Daniel Onguru, Lucy Kamau, Mark Nanyingi, George Ong'amo, Benson Estambale
BACKGROUND: Malaria causes the greatest public health burden in sub-Saharan Africa where high mortality occurs mainly in children under 5 years of age. Traditionally, malaria has been reported mainly in the lowlands endemic regions of western Kenya, while the highlands of the Rift Valley have been relatively free except for the sporadic epidemics in some areas. Baringo County is located in the Kenyan highlands. The county generally experiences seasonal transmission of malaria. A few hotspots which experience continuous malaria transmission in the county do however exist...
June 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28621040/bioactive-neolignans-and-other-compounds-from-magnolia-grandiflora-l-isolation-and-antiplasmodial-activity
#14
Abdul Latif, Yongle Du, Seema R Dalal, Emilio F Merino, Maria B Cassera, Michael Goetz, David G I Kingston
Bioassay-guided fractionation of a methanol extract of Magnolia grandiflora against Plasmodium falciparum yielded two new (1 and 2) and six known (3 - 8) bioactive compounds. The structures of the new compounds were assigned by mass spectrometric and 1D and 2D NMR data. Known compounds were identified by comparison of (1) H NMR and MS data with literature data. The two known neolignans 3 and 4 showed moderate antiplasmodial activity with IC50 values of 2.8 ± 0.1 and 3.4 ± 0.1 μM, respectively. Weak antiplasmodial activity was recorded for compounds 1, 2, 5, 6, 7 and 8, with IC50 values of 38 ± 2, 23 ± 2, 16...
June 16, 2017: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/28620583/engineering-of-genetically-arrested-parasites-gaps-for-a-precision-malaria-vaccine
#15
REVIEW
Oriana Kreutzfeld, Katja Müller, Kai Matuschewski
Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including Plasmodium species, the causative agents of malaria. Efficient elimination of Plasmodium liver stages prior to blood infection is one of the most promising malaria vaccine strategies. Here, we describe different genetically arrested parasites (GAPs) that have been engineered in Plasmodium berghei, P. yoelii and P. falciparum and compare their vaccine potential...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28619071/new-adenovirus-based-vaccine-vectors-targeting-pfs25-elicit-antibodies-that-inhibit-plasmodium-falciparum-transmission
#16
Kathleen A McGuire, Kazutoyo Miura, Christopher M Wiethoff, Kim C Williamson
BACKGROUND: An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, Pfs25, are known to block parasite development in the mosquito vector. However, in initial clinical trials the limited immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge. METHODS: Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime boost vaccination strategies to augment the immune response against Pfs25...
June 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28618269/red-blood-cell-invasion-by-the-malaria-parasite-is-coordinated-by-the-pfap2-i-transcription-factor
#17
Joana Mendonca Santos, Gabrielle Josling, Philipp Ross, Preeti Joshi, Lindsey Orchard, Tracey Campbell, Ariel Schieler, Ileana M Cristea, Manuel Llinás
Obligate intracellular parasites must efficiently invade host cells in order to mature and be transmitted. For the malaria parasite Plasmodium falciparum, invasion of host red blood cells (RBCs) is essential. Here we describe a parasite-specific transcription factor PfAP2-I, belonging to the Apicomplexan AP2 (ApiAP2) family, that is responsible for regulating the expression of genes involved in RBC invasion. Our genome-wide analysis by ChIP-seq shows that PfAP2-I interacts with a specific DNA motif in the promoters of target genes...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28618199/lipid-interactions-modulate-the-structural-and-antigenic-properties-of-the-c-terminal-domain-of-the-malaria-antigen-merozoite-surface-protein-2
#18
Sreedam C Das, Rodrigo A V Morales, Jeffrey Seow, Krishnarjuna Bankala, Ravindu Dissanayake, Robin F Anders, Christopher A MacRaild, Raymond S Norton
Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored antigen on the malaria parasite Plasmodium falciparum. MSP2 induces an immune response in the context of natural infections and vaccine trials, and these responses are associated with protection from parasite infection. Recombinant MSP2 is highly disordered in solution but antigenic analyses suggest that it is more ordered on the merozoite surface. We have shown previously that the interaction of recombinant full-length MSP2 with lipid surfaces induces a conformational change in the conserved N-terminal region of MSP2, which contributes to epitope masking in this region...
June 15, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28617253/the-emerging-role-of-the-human-bone-marrow-as-a-privileged-developmental-niche-for-the-transmission-stages-of-the-malaria-parasite-plasmodium-falciparum-commentary
#19
Pietro Alano
The spread of malaria relies on the ability of the Plasmodium parasites to be transmitted from infected individuals to the Anopheles mosquito vectors. Recent work on the most lethal of the malaria parasites, Plasmodium falciparum, identified the infected human bone marrow as a preferential site for the localization and maturation of the parasite transmission stages, the gametocytes. These findings unveil a complex host parasite interplay and an unsuspected role of the bone marrow microenvironment in the successful transmission of the malaria parasite and have major implications in developing and targeting future interventions to block the transmission of P...
April 2017: Annali Dell'Istituto Superiore di Sanità
https://www.readbyqxmd.com/read/28615843/in-vitro-adaptability-of-plasmodium-falciparum-to-different-fresh-serum-alternatives
#20
Chandrajit Dohutia, Pradyumna K Mohapatra, Dibya Ranjan Bhattacharyya, Kabita Gogoi, Khukumoni Bora, Basanta K Goswami
To reduce the dependency on fresh AB(+) serum in continuous culture of Plasmodium falciparum, a comparative study was undertaken to assess the in vitro adaptability of P. falciparum to media supplemented with fresh AB(+) serum from whole blood, AB(+) plasma, serum derived from AB(+) plasma, AB(+) human serum from Sigma, Albumax II, fetal bovine serum and new born calf serum, independently and in different combinations. Combinations were used to analyze whether two different substitutes demonstrate any synergistic effect on the growth of the parasites...
June 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
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