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p. falciparum

NOT Open Access | Compensating P. falciparum artemisinin resistance

December 14, 2021 - 20:59 -- NOT Open Access
Author(s): 
Platon L, Cao J, Ménard D
Reference: 
Cell Host Microbe. 2021 Dec 8;29(12):1732-1734

Amino acid deprivation from reduced hemoglobin degradation in Pfkelch13 artemisinin-resistant parasites reduces fitness.

Not Open Access | Analysis of sex-specific lipid metabolism of P. falciparum points to importance of sphingomyelin for gametocytogenesis

December 14, 2021 - 20:38 -- NOT Open Access
Author(s): 
Ridgway MC, Cihalova D, Brown SHJ, Tran P, Mitchell TW, Maier AG
Reference: 
J Cell Sci. 2021 Dec 9:jcs.259592

Male and female Plasmodium falciparum gametocytes are the parasite lifecycle stage responsible for transmission of malaria from the human host to mosquito vector. Not only are gametocytes able to survive in radically different host environments, but they are also precursors for male and female gametes that reproduce sexually soon after ingestion by the mosquito.

The Artemiside-Artemisox-Artemisone-M1 Tetrad: Efficacies against Blood Stage P. falciparum Parasites, DMPK Properties, and the Case for Artemiside

December 14, 2021 - 20:20 -- Open Access
Author(s): 
Gibhard L, Coertzen D, Reader J, Van der Watt ME, Birkholtz L, Wong HN, Batty KT, Haynes RK, Wiesner L
Reference: 
Pharmaceutics 2021, 13(12), 2066

Because of the need to replace the current clinical artemisinins in artemisinin combination therapies, we are evaluating fitness of amino-artemisinins for this purpose. These include the thiomorpholine derivative artemiside obtained in one scalable synthetic step from dihydroartemisinin (DHA) and the derived sulfone artemisone. We have recently shown that artemiside undergoes facile metabolism via the sulfoxide artemisox into artemisone and thence into the unsaturated metabolite M1; DHA is not a metabolite.

NOT Open Access | Structure, Function, and Thermodynamics of Lactate Dehydrogenases from Humans and the Malaria Parasite P. falciparum

November 10, 2021 - 21:06 -- NOT Open Access
Author(s): 
Khrapunov S, Waterman A, Persaud R, Chang EP
Reference: 
Biochemistry. 2021 Nov 8

Temperature adaptation is ubiquitous among all living organisms, yet the molecular basis for this process remains poorly understood. It can be assumed that for parasite-host systems, the same enzymes found in both organisms respond to the same selection factor (human body temperature) with similar structural changes. Herein, we report the existence of a reversible temperature-dependent structural transition for the glycolytic enzyme lactate dehydrogenase (LDH) from the malaria parasite Plasmodium falciparum (pfLDH) and human heart (hhLDH) occurring in the temperature range of human fever.

Osteopontin and malaria: no direct effect on parasite growth, but correlation with P. falciparum-specific B cells and BAFF in a malaria endemic area

November 10, 2021 - 20:59 -- Open Access
Author(s): 
Mortazavi SE, Lugaajju A, Kaddumukasa M, Tijani MK, Kironde F, Persson KEM
Reference: 
BMC Microbiol. 2021 Nov 6;21(1):307

The dysregulation of B cell activation is prevalent during naturally acquired immunity against malaria. Osteopontin (OPN), a protein produced by various cells including B cells, is a phosphorylated glycoprotein that participates in immune regulation and has been suggested to be involved in the immune response against malaria. Here we studied the longitudinal concentrations of OPN in infants and their mothers living in Uganda, and how OPN concentrations correlated with B cell subsets specific for P. falciparum and B cell activating factor (BAFF). We also investigated the direct effect of OPN on P. falciparum in vitro.

Real-time PCR assays for detection and quantification of early P. falciparum gametocyte stages

October 5, 2021 - 10:50 -- Open Access
Author(s): 
Gadalla AAH, Siciliano G, Farid R, Alano P, Ranford-Cartwright L, McCarthy JS, Thompson J, Babiker HA
Reference: 
Sci Rep. 2021 Sep 27;11(1):19118

The use of quantitative qRT-PCR assays for detection and quantification of late gametocyte stages has revealed the high transmission capacity of the human malaria parasite, Plasmodium falciparum. To understand how the parasite adjusts its transmission in response to in-host environmental conditions including antimalarials requires simultaneous quantification of early and late gametocytes.

Not Open Access | KAHRP dynamically relocalizes to remodeled actin junctions and associates with knob spirals in P. falciparum-infected erythrocytes

September 14, 2021 - 14:36 -- NOT Open Access
Author(s): 
Sanchez CP, Patra P, Chang SS, Karathanasis C, Hanebutte L, Kilian N, Cyrklaff M, Heilemann M, Schwarz US, Kudryashev M, Lanzer M
Reference: 
Mol Microbiol. 2021 Sep 13

The knob-associated histidine-rich protein (KAHRP) plays a pivotal role in the pathophysiology of Plasmodium falciparum malaria by forming membrane protrusions in infected erythrocytes, which anchor parasite-encoded adhesins to the membrane skeleton. The resulting sequestration of parasitized erythrocytes in the microvasculature leads to severe disease. Despite KAHRP being an important virulence factor, its physical location within the membrane skeleton is still debated, as is its function in knob formation.

Decreased parasite burden and altered host response in children with sickle cell anemia and severe anemia with malaria

September 8, 2021 - 15:56 -- Open Access
Author(s): 
Henrici RC, Sautter CL, Bond C, Opoka RO, Namazzi R, Datta D, Ware RE, Conroy AL, John CC
Reference: 
Blood Adv. 2021 Sep 1:bloodadvances.2021004704

Plasmodium falciparum malaria causes morbidity and mortality in African children with sickle cell anemia (SCA), but comparisons of host responses to P. falciparum between children with SCA (HbSS) and HbAA are limited. We assessed parasite biomass and plasma markers of inflammation and endothelial activation in children with HbAA (n=208) or HbSS (n=22) who presented with severe anemia and P. falciparum parasitemia to Mulago Hospital in Kampala, Uganda. Genotyping was performed at study completion.

Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes

August 25, 2021 - 16:18 -- Open Access
Author(s): 
Tuedom AGB, Sarah-Matio EM, Nsango SE, et al.
Reference: 
PLoS One. 2021 Aug 19;16(8):e0256343

The spread of Plasmodium falciparum resistant parasites remains one of the major challenges for malaria control and elimination in Sub Saharan Africa. Monitoring of molecular markers conferring resistance to different antimalarials is important to track the spread of resistant parasites and to optimize the therapeutic lifespan of current drugs. This study aimed to evaluate the prevalence of known mutations in the drug resistance genes Pfcrt, Pfmdr1, Pfdhfr and Pfdhps in two different epidemiological settings in Cameroon. Dried blood spots collected in 2018 and 2019 from asymptomatic individuals were used for DNA extraction and then the Plasmodium infection status was determined byPCR.

Neutrophils dominate in opsonic phagocytosis of P. falciparum blood-stage merozoites and protect against febrile malaria

August 25, 2021 - 15:58 -- Open Access
Author(s): 
Garcia-Senosiain A, Kana IH, Singh S, Das MK, Dziegiel MH, Hertegonne S, Adu B, Theisen M
Reference: 
Commun Biol. 2021 Aug 19;4(1):984

Antibody-mediated opsonic phagocytosis (OP) of Plasmodium falciparum blood-stage merozoites has been associated with protection against malaria. However, the precise contribution of different peripheral blood phagocytes in the OP mechanism remains unknown. Here, we developed an in vitro OP assay using peripheral blood leukocytes that allowed us to quantify the contribution of each phagocytic cell type in the OP of merozoites.

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