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plasmodium falciparum

Inhibition of Plasmepsin V Activity Blocks Plasmodium falciparum Gametocytogenesis and Transmission to Mosquitoes

January 15, 2020 - 09:25 -- Open Access
Author(s): 
Jennison C, Lucantoni L, O'Neill MT, McConville R, Erickson SM, Cowman AF, Sleebs BE, Avery VM, Boddey JA
Reference: 
Cell Reports Volume 29, ISSUE 12, P 3796-3806.e4 December 17, 2019

Plasmodium falciparum gametocytes infect mosquitoes and are responsible for malaria transmission. New interventions that block transmission could accelerate malaria elimination. Gametocytes develop within erythrocytes and activate protein export pathways that remodel the host cell. Plasmepsin V (PMV) is an aspartyl protease that is required for protein export in asexual parasites, but its function and essentiality in gametocytes has not been definitively proven, nor has PMV been assessed as a transmission-blocking drug target.

NOT Open Access | Autophagy-related protein PfATG18 participates in food vacuole dynamics and autophagy-like pathway in Plasmodium falciparum

January 15, 2020 - 09:17 -- NOT Open Access
Author(s): 
Agrawal P, Manjithaya R, Surolia N
Reference: 
Mol Microbiol, 2019 Dec 21.

Plasmodium falciparum has a limited repertoire of autophagy‐related genes (ATGs), and the functions of various proteins of the autophagy‐like pathway are not fully established in this protozoan parasite. Studies suggest that some of the autophagy proteins are crucial for parasite growth. PfATG18, for example, is essential for parasite replication and has a noncanonical role in apicoplast biogenesis. In this study, we demonstrate the conserved functions of PfATG18 in food vacuole (FV) dynamics and autophagy. Intriguingly, the P. falciparum FV is found to undergo fission and fusion and PfATG18 gets enriched at the interfaces of the newly generated multilobed FV during the process.

Evidence of positively selected G6PD A- allele reduces risk of Plasmodium falciparum infection in African population on Bioko Island

January 15, 2020 - 09:10 -- Open Access
Author(s): 
Liang XY, Chen JT, Ma YB, Huang HY, Xie DD, Monte-Nguba SM, Ehapo CS, Eyi UM, Zheng YZ, Liu XZ, Zha GC, Lin LY, Chen WZ, Zhou X, Lin M
Reference: 
Mol Genet Genomic Med. 2019 Dec 24:e1061

Glucose‐6‐phosphate dehydrogenase (G6PD) is an essential enzyme that protects red blood cells from oxidative damage. Although G6PD‐deficient alleles appear to confer a protective effect of malaria, the link with clinical protection against Plasmodium infection is conflicting.

Multigenic architecture of piperaquine resistance trait in Plasmodium falciparum

January 15, 2020 - 08:59 -- Open Access
Author(s): 
Silva M, Calçada C, Teixeira M, Veiga MI, Ferreira PE
Reference: 
Lancet Infect Dis. 2020 Jan; 20(1):26-27

William L Hamilton and colleagues1 and Rob W van der Pluijm and colleagues2 described the genomic evolution of Plasmodium falciparum malaria and the spread of resistance in this species to dihydroartemisinin–piperaquine in Southeast Asia. Resistance in the region has been associated with crt polymorphisms, 1, 2, 3 copy number variations in plasmepsins, 1, 2, 3, 4, 5 and mdr1 genes.4, 5

Lyse-Reseal Erythrocytes for Transfection of Plasmodium falciparum

January 15, 2020 - 07:56 -- Open Access
Author(s): 
Govindarajalu G, Rizvi Z, Kumar D, Sijwali PS
Reference: 
Scientific Reports, 2019 Dec 27; 9(1):19952

Simple and efficient transfection methods for genetic manipulation of Plasmodium falciparum are desirable to identify, characterize and validate the genes with therapeutic potential and better understand parasite biology. Among the available transfection techniques for P. falciparum, electroporation-based methods, particularly electroporation of ring-infected RBCs is routinely used.

NOT Open Access | The Structure of Plasmodium falciparum Hydroxymethyldihydropterin Pyrophosphokinase-Dihydropteroate Synthase Reveals the Basis of Sulfa Resistance

January 15, 2020 - 07:54 -- NOT Open Access
Author(s): 
Chitnumsub P, Jaruwat A, Talawanich Y, Noytanom K, Liwnaree B, Poen S, Yuthavong Y
Reference: 
FEBS J. 2019 Dec 28

The clinical efficacy of sulfa drugs as antimalarials has declined owing to the evolution of resistance in Plasmodium falciparum (Pf) malaria parasites. In order to understand the basis of this resistance and to design more effective antimalarials, we have solved thirteen structures of the bifunctional enzyme 6‐hydroxymethyl‐7,8‐dihydropterin pyrophosphokinase (HPPK)‐dihydropteroate synthase (DHPS) from wild‐type P. falciparum and sulfa‐resistant mutants, both as apo enzyme and as complexes with pteroate (PTA) and sulfa derivatives.

NOT Open Access | Discovery of potential 1,3,5-Triazine compounds against strains of Plasmodium falciparum using supervised machine learning models

January 15, 2020 - 07:53 -- NOT Open Access
Author(s): 
Sahu S, Ghosh SK, Kalita JM, Ginjupalli MC, K KR
Reference: 
European Journal of Pharmaceutical Sciences, Volume 144, 1 March 2020, 105208

The Malaria burden was an escalating global encumbrance and need to be addressed with critical care. Anti-malarial drug discovery was integrated with supervised machine learning (ML) models to identify potent thiazolyl-traizine derivatives. This assimilated approach of Direct Kernel-based Partial Least Squares regression (DKPLS) with molprint 2D fingerprints in Quantitative Structure Activity Relationship models was utilized to map the knowledge of known actives and to design novel molecules.

Diverse Antibody Responses to Conserved Structural Motifs in Plasmodium falciparum Circumsporozoite Protein

January 15, 2020 - 07:51 -- Open Access
Author(s): 
Pholcharee T, Oyen D, Torres JL, Flores-Garcia Y, Martin GM, González-Páez GE, Emerling D, Volkmuth W, Locke E, King CR, Zavala F, Ward AB, Wilson IA
Reference: 
J Mol Biol. 2019 Dec 27. pii: S0022-2836(19)30738-7

Malaria vaccine candidate RTS,S/AS01 is based on the central and C-terminal regions of the circumsporozoite protein (CSP) of P. falciparum. mAb397 was isolated from a volunteer in an RTS,S/AS01 clinical trial, and it protects mice from infection by malaria sporozoites. However, mAb397 originates from the less commonly used VH3-15 germline gene compared to the VH3-30/33 antibodies generally elicited by RTS,S to the central NANP repeat region of CSP. The crystal structure of mAb397 with an NPNA4 peptide shows that the central NPNA forms a type I β-turn and is the main recognition motif.

NOT Open Access | Targeting metacaspase-3 from Plasmodium falciparum towards antimalarial therapy: A combined approach of in-silico and in-vitro investigation

January 14, 2020 - 16:46 -- NOT Open Access
Author(s): 
Kumar B, Mohammad T, Amaduddin, Hussain A, Islam A, Ahmad F, Alajmi MF, Singh S, Pandey KC, Hassan MI, Abid M
Reference: 
Journal of Biomolecular Structure and Dynamics, 2020 Jan 13:1-10

Malaria is a global challenge, and its infection is propagated through Plasmodium falciparum, an obligate human parasite. The genome of P. falciparum encodes many proteases that play significant roles in their survival and pathogenesis thus being considered as attractive drug targets. P. falciparum metacaspase-3 (PfMCA3) is one such protease and a validated drug target to control malarial infection.

NOT Open Access | Using two phases of the CD4 T cell response to blood-stage murine malaria to understand regulation of systemic immunity and placental pathology in Plasmodium falciparum infection

January 14, 2020 - 16:30 -- NOT Open Access
Author(s): 
Gbedande K, Carpio VH, Stephens R
Reference: 
Immunological Reviews, Volume293, Issue1, January 2020, Pages 88-114

Plasmodium falciparum infection and malaria remain a risk for millions of children and pregnant women. Here, we seek to integrate knowledge of mouse and human T helper cell (Th) responses to blood‐stage Plasmodium infection to understand their contribution to protection and pathology. Although there is no complete Th subset differentiation, the adaptive response occurs in two phases in non‐lethal rodent Plasmodium infection, coordinated by Th cells.

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