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malaria parasites

Deliberately infecting healthy volunteers with malaria parasites: Perceptions and experiences of participants and other stakeholders in a Kenyan-based malaria infection study

July 13, 2020 - 16:19 -- Open Access
Jao I, Marsh V, Che Chi P, Kapulu M, Hamaluba M, Molyneux S, Bejon P, Kamuya D
Bioethics. 2020 Jul 9

Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders’ perceptions and experiences of deliberate infection and moral implications of these.

Genome wide distribution of G-quadruplexes and their impact on gene expression in malaria parasites

July 7, 2020 - 13:20 -- Open Access
Gazanion E, Lacroix L, Alberti P, Gurung P, Wein S, Cheng M, Mergny JL, Gomes AR, Lopez-Rubio JJ
PLoS Genet 16(7): e1008917

Mechanisms of transcriptional control in malaria parasites are still not fully understood. The positioning patterns of G-quadruplex (G4) DNA motifs in the parasite's AT-rich genome, especially within the var gene family which encodes virulence factors, and in the vicinity of recombination hotspots, points towards a possible regulatory role of G4 in gene expression and genome stability. Here, we carried out the most comprehensive genome-wide survey, to date, of G4s in the Plasmodium falciparum genome using G4Hunter, which identifies G4 forming sequences (G4FS) considering their G-richness and G-skewness.

Selective whole genome amplification of Plasmodium malariae DNA from clinical samples reveals insights into population structure

July 6, 2020 - 16:52 -- Open Access
Ibrahim A, Diez Benavente E, Campino S, et al.
Sci Rep. 2020 Jul 2;10(1):10832

The genomic diversity of Plasmodium malariae malaria parasites is understudied, partly because infected individuals tend to present with low parasite densities, leading to difficulties in obtaining sufficient parasite DNA for genome analysis. Selective whole genome amplification (SWGA) increases the relative levels of pathogen DNA in a clinical sample, but has not been adapted for P. malariae parasites.

Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

June 3, 2020 - 15:54 -- Open Access
Subudhi AK, O'Donnell AJ, Pain A, et al.
Nat Commun. 2020 Jun 2; 11(1):2763

Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown.

Rrp6 Regulates Heterochromatic Gene Silencing via ncRNA RUF6 Decay in Malaria Parasites

June 3, 2020 - 15:47 -- Open Access
Fan Y, Shen S, Zhang Q, et al.
mBio. 2020 Jun 2; 11(3):e01110-20

The heterochromatin environment plays a central role in silencing genes associated with the malaria parasite’s development, survival in the host, and transmission to the mosquito vector. However, the underlying mechanism regulating the dynamic chromatin structure is not understood yet. Here, we have uncovered that Plasmodium falciparum Rrp6, an orthologue of eukaryotic RNA exosome-associated RNase, controls the silencing of heterochromatic genes.

Not Open Access | Plastid biogenesis in malaria parasites requires the interactions and catalytic activity of the Clp proteolytic system

June 2, 2020 - 14:02 -- NOT Open Access
Florentin A, Stephens DR, Brooks CF, Baptista RP, Muralidharan V
Proc Natl Acad Sci U S A. 2020 Jun 1:201919501

The human malaria parasite, Plasmodium falciparum, contains an essential plastid called the apicoplast. Most apicoplast proteins are encoded by the nuclear genome and it is unclear how the plastid proteome is regulated. Here, we study an apicoplast-localized caseinolytic-protease (Clp) system and how it regulates organelle proteostasis. Using null and conditional mutants, we demonstrate that the P. falciparum Clp protease (PfClpP) has robust enzymatic activity that is essential for apicoplast biogenesis.

Directing Traffic: Chaperone-mediated protein transport in malaria parasites

May 13, 2020 - 14:00 -- Open Access
Florentin A, Cobb DW, Kudyba HM, Muralidharan V
Cell Microbiol. 2020 May 9:e13215

The ability of eukaryotic parasites from the phylum Apicomplexa to cause devastating diseases is predicated upon their ability to maintain faithful and precise protein trafficking mechanisms. Their parasitic life cycle depends on the trafficking of effector proteins to the infected host cell, transport of proteins to several critical organelles required for survival, as well as transport of parasite and host proteins to the digestive organelles to generate the building blocks for parasite growth.

Field evaluation of DNA detection of human filarial and malaria parasites using mosquito excreta/feces

April 13, 2020 - 14:05 -- Open Access
Minetti C, Pilotte N, Zulch M, Canelas T, Tettevi EJ, Veriegh FBD, Osei-Atweneboana MY, Williams SA, Reimer LJ
PLoS Negl Trop Dis. 2020 Apr 8;14(4):e0008175

We recently developed a superhydrophobic cone-based method for the collection of mosquito excreta/feces (E/F) for the molecular xenomonitoring of vector-borne parasites showing higher throughput compared to the traditional approach. To test its field applicability, we used this platform to detect the presence of filarial and malaria parasites in two villages of Ghana and compared results to those for detection in mosquito carcasses and human blood.

Lapatinib, Nilotinib and Lomitapide Inhibit Haemozoin Formation in Malaria Parasites

April 6, 2020 - 15:29 -- Open Access
de Sousa ACC, Maepa K, Combrinck JM, Egan TJ
Molecules. 2020 Mar 29;25(7). pii: E1571

With the continued loss of antimalarials to resistance, drug repositioning may have a role in maximising efficiency and accelerating the discovery of new antimalarial drugs. Bayesian statistics was previously used as a tool to virtually screen USFDA approved drugs for predicted β-haematin (synthetic haemozoin) inhibition and in vitro antimalarial activity.

Conserved associations between G-quadruplex-forming DNA motifs and virulence gene families in malaria parasites

March 23, 2020 - 11:21 -- Open Access
Gage HL, Merrick CJ
BMC Genomics. 2020 Mar 17;21(1):236

The Plasmodium genus of malaria parasites encodes several families of antigen-encoding genes. These genes tend to be hyper-variable, highly recombinogenic and variantly expressed. The best-characterized family is the var genes, exclusively found in the Laveranian subgenus of malaria parasites infecting humans and great apes. Var genes encode major virulence factors involved in immune evasion and the maintenance of chronic infections. In the human parasite P. falciparum, var gene recombination and diversification appear to be promoted by G-quadruplex (G4) DNA motifs, which are strongly associated with var genes in P. falciparum. Here, we investigated how this association might have evolved across Plasmodium species – both Laverania and also more distantly related species which lack vars but encode other, more ancient variant gene families.


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