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https://www.readbyqxmd.com/read/29029367/genetic-diversity-of-plasmodium-falciparum-merozoite-surface-protein-1-block-2-glutamate-rich-protein-and-sexual-stage-antigen-pfs25-from-chandigarh-north-india
#1
Hargobinder Kaur, Rakesh Sehgal, Kapil Goyal, Nikita Makkar, Richa Yadav, Praveen K Bharti, Neeru Singh, Nilanju P Sarmah, Pradymna K Mohapatra, Jagadish Mahanta, Devendra Bansal, Ali A Sultan, Jagat R Kanwar
OBJECTIVE: To elucidate the genetic diversity of P. falciparum in residual transmission foci of northern India. METHODS: Clinically suspected malaria patients were screened for malaria infection by microscopy. 48 P. falciparum-infected patients were enrolled from two tertiary care hospitals in Chandigarh, India. Blood samples were collected from enrolled patients, genomic DNA extraction and nested PCR was performed for further species confirmation. Sanger sequencing was carried out using block 2 region of msp1, R2 region of glurp and pfs25 specific primers...
October 13, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28993460/evaluation-of-a-plasmodium-specific-carrier-protein-to-enhance-production-of-recombinant-pfs25-a-leading-transmission-blocking-vaccine-candidate
#2
Elizabeth M Parzych, Kazutoyo Miura, Aarti Ramanathan, Carole A Long, James M Burns
Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multi-antigen vaccine. Attempting to resolve these issues, we focused on the use of the highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that genetic fusion of the C-terminal 19 kDa fragment of merozoite surface protein 1 (MSP119) to PfMSP8 facilitated antigen production, folding and induction of neutralizing antibodies to conformational B cell epitopes of MSP119 Here, using the PfMSP1/8 construct, we further optimized the rPfMSP8 carrier by introduction of two cysteine to serine substitutions (CΔS) to improve the yield of monomeric product...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28985225/disrupting-assembly-of-the-inner-membrane-complex-blocks-plasmodium-falciparum-sexual-stage-development
#3
Molly Parkyn Schneider, Boyin Liu, Philipp Glock, Annika Suttie, Emma McHugh, Dean Andrew, Steven Batinovic, Nicholas Williamson, Eric Hanssen, Paul McMillan, Marion Hliscs, Leann Tilley, Matthew W A Dixon
Transmission of malaria parasites relies on the formation of a specialized blood form called the gametocyte. Gametocytes of the human pathogen, Plasmodium falciparum, adopt a crescent shape. Their dramatic morphogenesis is driven by the assembly of a network of microtubules and an underpinning inner membrane complex (IMC). Using super-resolution optical and electron microscopies we define the ultrastructure of the IMC at different stages of gametocyte development. We characterize two new proteins of the gametocyte IMC, called PhIL1 and PIP1...
October 6, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28985216/the-babesia-bovis-hap2-gene-is-not-required-for-blood-stage-replication-but-expressed-upon-in-vitro-sexual-stage-induction
#4
Hala E Hussein, Reginaldo G Bastos, David A Schneider, Wendell C Johnson, Fatma K Adham, William C Davis, Jacob M Laughery, David R Herndon, Heba F Alzan, Massaro W Ueti, Carlos E Suarez
Babesia bovis, is a tick borne apicomplexan parasite responsible for important cattle losses globally. Babesia parasites have a complex life cycle including asexual replication in the mammalian host and sexual reproduction in the tick vector. Novel control strategies aimed at limiting transmission of the parasite are needed, but transmission blocking vaccine candidates remain undefined. Expression of HAP2 has been recognized as critical for the fertilization of parasites in the Babesia-related Plasmodium, and is a leading candidate for a transmission blocking vaccine against malaria...
October 6, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28976194/angeloylated-germacranolides-from-daucus-virgatus-and-their-plasmodium-transmission-blocking-activity
#5
Carmina Sirignano, Alì Snene, Daniela Rigano, Sofia Tapanelli, Carmen Formisano, Paolo Luciano, Ridha El Mokni, Saoussen Hammami, Alain Rodrigue Tenoh, Annette Habluetzel, Orazio Taglialatela-Scafati
Phytochemical investigation of the aerial parts of the Tunisian plant Daucus virgatus led to the isolation of eight new germacranolides named daucovirgolides A-H (1-8). The stereostructures of these sesquiterpene lactones, decorated by either one or two angeloyl groups, have been determined by a combination of MS, NMR spectroscopy, chemical derivatization, and comparison of experimental electronic circular dichroism curves with TDDFT-predicted data. Daucovirgolide G (7) proved to be the single member of this family to possess a marked inhibitory activity (92% at 50 μg/mL) on the development of Plasmodium early sporogonic stages, the nonpathogenic transmissible stages of malaria parasites, devoid of general cytotoxicity...
October 4, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28965427/malaria-medicines-to-address-drug-resistance-and-support-malaria-elimination-efforts
#6
Jane Achan, Julia Mwesigwa, Chinagozi Precious Edwin, Umberto D'alessandro
Antimalarial drugs are essential weapons to fight malaria and have been used effectively since the 17(th) century. However, P.falciparum resistance has been reported to almost all available antimalarial drugs, including artemisinin derivatives, raising concerns that this could jeopardize malaria elimination. Areas covered: In this article, we present a historical perspective of antimalarial drug resistance, review current evidence of resistance to available antimalarial drugs and discuss possible mitigating strategies to address this challenge...
October 11, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28939120/synthesis-characterization-and-cellular-localization-of-a-fluorescent-probe-of-the-antimalarial-8-aminoquinoline-primaquine
#7
Adonis McQueen, Lynn D Blake, Ala Azhari, M Trent Kemp, Tommy W McGaha, Niranjan Namelikonda, Randy W Larsen, Roman Manetsch, Dennis E Kyle
Primaquine (PQ) is the only commercially available drug that clears dormant liver stages of malaria and blocks transmission to mosquito vectors. Although an old drug, much remains to be known about the mechanism(s) of action. Herein we develop a fluorescent tagged PQ to discover cellular localization in the human malaria parasite, Plasmodium falciparum. Successful synthesis and characterization of a primaquine-coumarin fluorescent probe (PQCP) demonstrated potency equivalent to the parent drug and the probe was not cytotoxic to HepG2 carcinoma cells...
October 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28938876/assessment-of-the-effect-of-larval-source-management-and-house-improvement-on-malaria-transmission-when-added-to-standard-malaria-control-strategies-in-southern-malawi-study-protocol-for-a-cluster-randomised-controlled-trial
#8
Robert S McCann, Henk van den Berg, Peter J Diggle, Michèle van Vugt, Dianne J Terlouw, Kamija S Phiri, Aurelio Di Pasquale, Nicolas Maire, Steven Gowelo, Monicah M Mburu, Alinune N Kabaghe, Themba Mzilahowa, Michael G Chipeta, Willem Takken
BACKGROUND: Due to outdoor and residual transmission and insecticide resistance, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) will be insufficient as stand-alone malaria vector control interventions in many settings as programmes shift toward malaria elimination. Combining additional vector control interventions as part of an integrated strategy would potentially overcome these challenges. Larval source management (LSM) and structural house improvements (HI) are appealing as additional components of an integrated vector management plan because of their long histories of use, evidence on effectiveness in appropriate settings, and unique modes of action compared to LLINs and IRS...
September 22, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28935916/infectious-disease-blocking-malaria-transmission
#9
Sarah Crunkhorn
No abstract text is available yet for this article.
October 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28932814/the-gut-commensal-microbiome-of-drosophila-melanogaster-is-modified-by-the-endosymbiont-wolbachia
#10
Rama K Simhadri, Eva M Fast, Rong Guo, Michaela J Schultz, Natalie Vaisman, Luis Ortiz, Joanna Bybee, Barton E Slatko, Horacio M Frydman
Endosymbiotic Wolbachia bacteria and the gut microbiome have independently been shown to affect several aspects of insect biology, including reproduction, development, life span, stem cell activity, and resistance to human pathogens, in insect vectors. This work shows that Wolbachia bacteria, which reside mainly in the fly germline, affect the microbial species present in the fly gut in a lab-reared strain. Drosophila melanogaster hosts two main genera of commensal bacteria-Acetobacter and Lactobacillus. Wolbachia-infected flies have significantly reduced titers of Acetobacter...
September 2017: MSphere
https://www.readbyqxmd.com/read/28923023/comparative-transcriptomics-of-female-and-male-gametocytes-in-plasmodium-berghei-and-the-evolution-of-sex-in-alveolates
#11
Lee M Yeoh, Christopher D Goodman, Vanessa Mollard, Geoffrey I McFadden, Stuart A Ralph
BACKGROUND: The clinical symptoms of malaria are caused by the asexual replication of Plasmodium parasites in the blood of the vertebrate host. To spread to new hosts, however, the malaria parasite must differentiate into sexual forms, termed gametocytes, which are ingested by a mosquito vector. Sexual differentiation produces either female or male gametocytes, and involves significant morphological and biochemical changes. These transformations prepare gametocytes for the rapid progression to gamete formation and fertilisation, which occur within 20 min of ingestion...
September 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28886443/antiplasmodial-activities-of-dyes-against-plasmodium-falciparum-asexual-and-sexual-stages-contrasted-uptakes-of-triarylmethanes-brilliant-green-green-s-e142-and-patent-blue-v-e131-by-erythrocytes
#12
Louis-Jérôme Leba, Jean Popovici, Yannick Estevez, Stéphane Pelleau, Eric Legrand, Lise Musset, Christophe Duplais
The search for safe antimalarial compounds acting against asexual symptom-responsible stages and sexual transmission-responsible forms of Plasmodium species is one of the major challenges in malaria elimination programs. So far, among current drugs approved for human use, only primaquine has transmission-blocking activity. The discovery of small molecules targeting different Plasmodium falciparum life stages remains a priority in antimalarial drug research. In this context, several independent studies have recently reported antiplasmodial and transmission-blocking activities of commonly used stains, dyes and fluorescent probes against P...
August 2, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28874661/a-potent-series-targeting-the-malarial-cgmp-dependent-protein-kinase-clears-infection-and-blocks-transmission
#13
David A Baker, Lindsay B Stewart, Jonathan M Large, Paul W Bowyer, Keith H Ansell, María B Jiménez-Díaz, Majida El Bakkouri, Kristian Birchall, Koen J Dechering, Nathalie S Bouloc, Peter J Coombs, David Whalley, Denise J Harding, Ela Smiljanic-Hurley, Mary C Wheldon, Eloise M Walker, Johannes T Dessens, María José Lafuente, Laura M Sanz, Francisco-Javier Gamo, Santiago B Ferrer, Raymond Hui, Teun Bousema, Iñigo Angulo-Barturén, Andy T Merritt, Simon L Croft, Winston E Gutteridge, Catherine A Kettleborough, Simon A Osborne
To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28873011/response-to-blood-meal-in-the-fat-body-of-anopheles-stephensi-using-quantitative-proteomics-toward-new-vector-control-strategies-against-malaria
#14
Manish Kumar, Ajeet Kumar Mohanty, Sreelakshmi K Sreenivasamurthy, Gourav Dey, Jayshree Advani, Sneha M Pinto, Ashwani Kumar, Thottethodi Subrahmanya Keshava Prasad
Malaria remains a grand challenge for disruptive innovation in global health therapeutics and diagnostics. Anopheles stephensi is one of the major vectors of malaria in Asia. Vector and transmission control are key focus areas in the fight against malaria, a field of postgenomics research where proteomics can play a substantive role. Moreover, to identify novel strategies to control the vector population, it is necessary to understand the vector life processes at a global and molecular scale. In this context, fat body is a vital organ required for vitellogenesis, vector immunity, vector physiology, and vector-parasite interaction...
September 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28851851/multifunctional-involvement-of-a-c2h2-zinc-finger-protein-pbzfp-in-malaria-transmission-histone-modification-and-susceptibility-to-dna-damage-response
#15
Anusha M Gopalakrishnan, Ahmed S I Aly, L Aravind, Nirbhay Kumar
In sexually reproducing organisms, meiosis is an essential step responsible for generation of haploid gametes from diploid somatic cells. The quest for understanding regulatory mechanisms of meiotic recombination in Plasmodium led to identification of a gene encoding a protein that contains 11 copies of C2H2 zinc fingers (ZnF). Reverse genetic approaches were used to create Plasmodium berghei parasites either lacking expression of full-length Plasmodium berghei zinc finger protein (PbZfp) (knockout [KO]) or expressing PbZfp lacking C-terminal zinc finger region (truncated [Trunc])...
August 29, 2017: MBio
https://www.readbyqxmd.com/read/28820722/house-structure-is-associated-with-plasmodium-falciparum-infection-in-a-low-transmission-setting-in-southern-zambia
#16
Matthew M Ippolito, Kelly M Searle, Harry Hamapumbu, Timothy M Shields, Jennifer C Stevenson, Philip E Thuma, William J Moss, For The Southern Africa International Center Of Excellence For Malaria Research
House structure may influence the risk of malaria by affecting mosquito entry and indoor resting. Identification of construction features associated with protective benefits could inform vector control approaches, even in low-transmission settings. We examined the association between house structure and malaria prevalence in a cross-sectional analysis of 2,788 children and adults residing in 866 houses in a low-transmission area of Southern Province, Zambia, over the period 2008-2012. Houses were categorized according to wall (brick/cement block or mud/grass) and roof (metal or grass) material...
August 7, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28814310/modelling-the-benefits-of-long-acting-or-transmission-blocking-drugs-for-reducing-plasmodium-falciparum-transmission-by-case-management-or-by-mass-treatment
#17
Michael T Bretscher, Jamie T Griffin, Azra C Ghani, Lucy C Okell
BACKGROUND: Anti-malarial drugs are an important tool for malaria control and elimination. Alongside their direct benefit in the treatment of disease, drug use has a community-level effect, clearing the reservoir of infection and reducing onward transmission of the parasite. Different compounds potentially have different impacts on transmission-with some providing periods of prolonged chemoprophylaxis whilst others have greater transmission-blocking potential. The aim was to quantify the relative benefit of such properties for transmission reduction to inform target product profiles in the drug development process and choice of first-line anti-malarial treatment in different endemic settings...
August 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28808258/hexahydroquinolines-are-antimalarial-candidates-with-potent-blood-stage-and-transmission-blocking-activity
#18
Manu Vanaerschot, Leonardo Lucantoni, Tao Li, Jill M Combrinck, Andrea Ruecker, T R Santha Kumar, Kelly Rubiano, Pedro E Ferreira, Giulia Siciliano, Sonia Gulati, Philipp P Henrich, Caroline L Ng, James M Murithi, Victoria C Corey, Sandra Duffy, Ori J Lieberman, M Isabel Veiga, Robert E Sinden, Pietro Alano, Michael J Delves, Kim Lee Sim, Elizabeth A Winzeler, Timothy J Egan, Stephen L Hoffman, Vicky M Avery, David A Fidock
Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes...
August 14, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28800735/life-span-of-in-vitro-differentiated-plasmodium-falciparum-gametocytes
#19
Tamirat Gebru, Albert Lalremruata, Peter G Kremsner, Benjamin Mordmüller, Jana Held
BACKGROUND: The sexual stages (gametocytes) of Plasmodium falciparum do not directly contribute to the pathology of malaria but are essential for transmission of the parasite from the human host to the mosquito. Mature gametocytes circulate in infected human blood for several days and their circulation time has been modelled mathematically from data of previous in vivo studies. This is the first time that longevity of gametocytes is studied experimentally in vitro. METHODS: The in vitro longevity of P...
August 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28791254/transcriptional-profiling-defines-histone-acetylation-as-a-regulator-of-gene-expression-during-human-to-mosquito-transmission-of-the-malaria-parasite-plasmodium-falciparum
#20
Che J Ngwa, Meike J Kiesow, Olga Papst, Lindsey M Orchard, Michael Filarsky, Alina N Rosinski, Till S Voss, Manuel Llinás, Gabriele Pradel
Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by the intraerythrocytic gametocytes, which, once taken up during a blood meal, become activated to initiate sexual reproduction. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they are crucial for spreading the tropical disease. During gametocyte maturation, different repertoires of genes are switched on and off in a well-coordinated sequence, pointing to regulatory mechanisms of gene expression...
2017: Frontiers in Cellular and Infection Microbiology
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