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NOT Open Access | Characterization of mitochondrial carrier proteins of malaria parasite Plasmodium falciparum based on in vitro translation and reconstitution

June 26, 2020 - 15:34 -- NOT Open Access
Nozawa A, Ito D, Ibrahim M, Santos HJ, Tsuboi T, Tozawa Y
Parasitol Int. 2020 Jun 20:102160

Members of the mitochondrial carrier (MC) family of membrane transporters play important roles in cellular metabolism. We previously established an in vitro reconstitution system for membrane transporters based on wheat germ cell-free translation system. We have now applied this reconstitution system to the comparative analysis of MC proteins from the malaria parasite Plasmodium falciparum and Saccharomyces cerevisiae. We synthesized twelve putative P. falciparum MCs and determined the transport activities of four of these proteins including PF3D7_1037300 protein (ADP/ATP translocator), PF3D7_1004800 protein (ADP/ATP translocator), PF3D7_1,202,200 protein (phosphate carrier), and PF3D7_1241600 protein (S-adenosylmethionine transporter).

Structure-Based Identification and Functional Characterization of a Lipocalin in the Malaria Parasite Plasmodium falciparum

June 26, 2020 - 12:04 -- Open Access
Burda PC, Crosskey T, Gilberger TW, et al.
Cell Rep. 2020 Jun 23; 31(12):107817

Proteins of the lipocalin family are known to bind small hydrophobic ligands and are involved in various physiological processes ranging from lipid transport to oxidative stress responses. The genome of the malaria parasite Plasmodium falciparum contains a single protein PF3D7_0925900 with a lipocalin signature. Using crystallography and small-angle X-ray scattering, we show that the protein has a tetrameric structure of typical lipocalin monomers; hence we name it P. falciparum lipocalin (PfLCN).

A divergent cyclin/cyclin-dependent kinase complex controls the atypical replication of a malaria parasite during gametogony and transmission

June 23, 2020 - 16:25 -- Open Access
Balestra AC, Zeeshan M, Brochet M, et al.
Elife. 2020 Jun 22; 9:e56474.

Cell cycle transitions are generally triggered by variation in the activity of cyclin-dependent kinases (CDKs) bound to cyclins. Malaria-causing parasites have a life cycle with unique cell-division cycles, and a repertoire of divergent CDKs and cyclins of poorly understood function and interdependency. We show that Plasmodium berghei CDK-related kinase 5 (CRK5), is a critical regulator of atypical mitosis in the gametogony and is required for mosquito transmission.

Ultrastructural alterations in Plasmodium falciparum induced by chalcone derivatives

June 17, 2020 - 12:54 -- Open Access
Sinha S, Radotra BD, Medhi B, Batovska DI, Markova N, Sehgal R
BMC Res Notes. 2020 Jun 15; 13(1):290

Chalcones (1, 3-diaryl-2-propen-1-ones) and their derivatives are widely explored from the past decade for its antimalarial activity. To elucidate their mechanism of action on the malaria parasite, the ultrastructural changes with the action of these derivatives in different organelles of the parasite were studied in vitro. Infected RBCs [CQ sensitive (MRC-2) and CQ resistant (RKL-9) Plasmodium strain] were treated with three chalcone derivatives 1, 2 and 3 and standard drugs, i.e., CQ and artemisinin at twice their respective IC50 values for 24 h and then harvested, washed, fixed, embedded and stained to visualize ultra-structure changes before and after intervention of treatment under in vitro condition through transmission electron microscope.

NOT Open Access | Rab7 of Plasmodium falciparum is involved in its retromer complex assembly near the digestive vacuole

June 9, 2020 - 15:34 -- NOT Open Access
Siddiqui AA, Saha D, Iqbal MS, Saha SJ, Sarkar S, Banerjee C, Nag S, Mazumder S, De R, Pramanik S, Debsharma S, Bandyopadhyay U
Biochim Biophys Acta Gen Subj. 2020 Jun 5:129656

Intracellular protein trafficking is crucial for survival of cell and proper functioning of the organelles; however, these pathways are not well studied in the malaria parasite. Its unique cellular architecture and organellar composition raise an interesting question to investigate.

NOT Open Access | Insulin signalling in RBC is responsible for growth stimulation of malaria parasite in diabetes patients

June 9, 2020 - 11:18 -- NOT Open Access
Balaji SN, Sahasrabuddhe AA, Trivedi V
Biochem Biophys Res Commun. 2020 Jun 3:S0006-291X(20)31090-1

A cross-talk between diabetes and malaria within-host is well established. Diabetes is associated with modulation of the immune system, impairment of the healing process and to disturb the host metabolism to contribute towards propagation of parasite infection. Glucose metabolism in host is maintained by insulin and RBC has 2000 insulin receptor present on plasma membrane.

Targeted repression of Plasmodium apicortin by host microRNA impairs malaria parasite growth and invasion

June 6, 2020 - 15:05 -- Open Access
Chakrabarti M, Garg S, Rajagopal A, Pati S, Singh S
Dis Model Mech. 2020 Jun 3;13(6):dmm042820

Mature human erythrocytes contain a rich pool of microRNAs (miRNAs), which result from differentiation of the erythrocytes during the course of haematopoiesis. Recent studies have described the effect of erythrocytic miRNAs on the invasion and growth of the malaria parasite Plasmodium falciparum during the asexual blood stage of its life cycle. In this work, we have identified two erythrocytic miRNAs, miR-150-3p and miR-197-5p, that show favourable in silico hybridization with Plasmodium apicortin, a protein with putative microtubule-stabilizing properties.

Zygote morphogenesis but not the establishment of cell polarity in Plasmodium berghei is controlled by the small GTPase, RAB11A

June 1, 2020 - 16:01 -- Open Access
Patil H, Hughes KR, Lemgruber L, Philip N, Dickens N, Starnes GL, Waters AP
PLoS Pathog 16(5): e1008091

Plasmodium species are apicomplexan parasites whose zoites are polarized cells with a marked apical organisation where the organelles associated with host cell invasion and colonization reside. Plasmodium gametes mate in the mosquito midgut to form the spherical and presumed apolar zygote that morphs during the following 24 hours into a polarized, elongated and motile zoite form, the ookinete. Endocytosis-mediated protein transport is generally necessary for the establishment and maintenance of polarity in epithelial cells and neurons, and the small GTPase RAB11A is an important regulator of protein transport via recycling endosomes.

An open-label phase 1/2a trial of a genetically modified rodent malaria parasite for immunization against Plasmodium falciparum malaria

May 25, 2020 - 07:26 -- Open Access
Reuling IJ, Mendes AM, Prudêncio M, et al.
Science Translational Medicine, 20 May 2020: Vol. 12, Issue 544, eaay2578

For some diseases, successful vaccines have been developed using a nonpathogenic counterpart of the causative microorganism of choice. The nonpathogenicity of the rodent Plasmodium berghei (Pb) parasite in humans prompted us to evaluate its potential as a platform for vaccination against human infection by Plasmodium falciparum (Pf), a causative agent of malaria. We hypothesized that the genetic insertion of a leading protein target for clinical development of a malaria vaccine, Pf circumsporozoite protein (CSP), in its natural pre-erythrocytic environment, would enhance Pb’s capacity to induce protective immunity against Pf infection.

Stochastic bond dynamics facilitates alignment of malaria parasite at erythrocyte membrane upon invasion

May 19, 2020 - 15:29 -- Open Access
Hillringhaus S, Dasanna AK, Gompper G, Fedosov DA
Elife. 2020 May 18;9. pii: e56500

Malaria parasites invade healthy red blood cells (RBCs) during the blood stage of the disease. Even though parasites initially adhere to RBCs with a random orientation, they need to align their apex toward the membrane in order to start the invasion process. Using hydrodynamic simulations of a RBC and parasite, where both interact through discrete stochastic bonds, we show that parasite alignment is governed by the combination of RBC membrane deformability and dynamics of adhesion bonds.


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