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parasites

NOT Open Access | A Novel Antiparasitic Compound Kills Ring-Stage Plasmodium falciparum and Retains Activity Against Artemisinin-Resistant Parasites

March 9, 2020 - 13:41 -- NOT Open Access
Author(s): 
Clements RL, Streva V, Dumoulin P, Huang W, Owens E, Raj DK, Burleigh B, Llinás M, Winzeler EA, Zhang Q, Dvorin JD
Reference: 
The Journal of Infectious Diseases, Volume 221, Issue 6, 15 March 2020, Pages 956–962

Spreading antimalarial resistance threatens effective treatment of malaria, an infectious disease caused by Plasmodium parasites. We identified a compound, BCH070, that inhibits asexual growth of multiple antimalarial-resistant strains of Plasmodium falciparum (half maximal inhibitory concentration [IC50] = 1–2 µM), suggesting that BCH070 acts via a novel mechanism of action.

Not Open Access | The Antimalarial Natural Product Salinipostin A Identifies Essential α/β Serine Hydrolases Involved in Lipid Metabolism in P. falciparum Parasites

February 24, 2020 - 13:40 -- NOT Open Access
Author(s): 
Yoo E, Schulze CJ, Stokes BH, Onguka O, Yeo T, Mok S, Gnädig NF, Zhou Y, Kurita K, Foe IT, Terrell SM, Boucher MJ, Cieplak P, Kumpornsin K, Lee MCS, Linington RG, Long JZ, Uhlemann AC, Weerapana E, Fidock DA, Bogyo M
Reference: 
Cell Chem Biol. 2020 Feb 20;27(2):143-157.e5

Salinipostin A (Sal A) is a potent antiplasmodial marine natural product with an undefined mechanism of action. Using a Sal A-derived activity-based probe, we identify its targets in the Plasmodium falciparum parasite. All of the identified proteins contain α/β serine hydrolase domains and several are essential for parasite growth. One of the essential targets displays a high degree of homology to human monoacylglycerol lipase (MAGL) and is able to process lipid esters including a MAGL acylglyceride substrate.

Epigenetic inhibitors target multiple stages of Plasmodium falciparum parasites

February 14, 2020 - 17:04 -- Open Access
Author(s): 
Coetzee N, von Grüning H, Opperman D, van der Watt M, Reader J, Birkholtz LM
Reference: 
Sci Rep. 2020 Feb 11; 10(1):2355

The epigenome of the malaria parasite, Plasmodium falciparum, is associated with regulation of various essential processes in the parasite including control of proliferation during asexual development as well as control of sexual differentiation. The unusual nature of the epigenome has prompted investigations into the potential to target epigenetic modulators with novel chemotypes. Here, we explored the diversity within a library of 95 compounds, active against various epigenetic modifiers in cancerous cells, for activity against multiple stages of P. falciparum development.

NOT Open Access | Developments in drug design strategies for bromodomain protein inhibitors to target Plasmodium falciparum parasites

December 30, 2019 - 15:16 -- NOT Open Access
Author(s): 
Nguyen HHT, Yeoh LM, Chisholm SA, Duffy MF
Reference: 
Expert Opin Drug Discov. 2019 Dec 23:1-11

Bromodomains (BRDs) bind to acetylated lysine residues, often on histones. The BRD proteins can contribute to gene regulation either directly through enzymatic activity or indirectly through recruitment of chromatin-modifying complexes or transcription factors. There is no evidence of direct orthologues of the Plasmodium falciparum BRD proteins (PfBDPs) outside the apicomplexans. PfBDPs are expressed during the parasite’s life cycle in both the human host’s blood and in the mosquito. PfBDPs could also prove to be promising targets for novel antimalarials, which are urgently required to address increasing drug resistance.

Immunity against sexual stage Plasmodium falciparum and Plasmodium vivax parasites

December 23, 2019 - 14:55 -- Open Access
Author(s): 
de Jong RM, Tebeje SK, Meerstein-Kessel L, Tadesse FG, Jore MM, Stone W, Bousema T
Reference: 
Immunol Rev. 2019 Dec 16.

The efficient spread of malaria from infected humans to mosquitoes is a major challenge for malaria elimination initiatives. Gametocytes are the only Plasmodium life stage infectious to mosquitoes. Here, we summarize evidence for naturally acquired anti‐gametocyte immunity and the current state of transmission blocking vaccines (TBV). Although gametocytes are intra‐erythrocytic when present in infected humans, developing Plasmodium falciparum gametocytes may express proteins on the surface of red blood cells that elicit immune responses in naturally exposed individuals.

What functional genomics has taught us about transcriptional regulation in malaria parasites

November 26, 2019 - 18:03 -- Open Access
Author(s): 
Christa G Toenhake, Richárd Bártfai
Reference: 
Briefings in Functional Genomics, Volume 18, Issue 5, September 2019, Pages 290–301

Malaria parasites are characterized by a complex life cycle that is accompanied by dynamic gene expression patterns. The factors and mechanisms that regulate gene expression in these parasites have been searched for even before the advent of next generation sequencing technologies. Functional genomics approaches have substantially boosted this area of research and have yielded significant insights into the interplay between epigenetic, transcriptional and post-transcriptional mechanisms.

Not Open Access | Dual regulatory effects of non-coding GC-rich elements on the expression of virulence genes in malaria parasites

November 16, 2015 - 14:24 -- NOT Open Access
Author(s): 
Guiying Wei, Yuemeng Zhao, Qingfeng Zhang, Weiqing Pan
Reference: 
Infection, Genetics and Evolution, Volume 36, December 2015, Pages 490-499

Here, we report a monoallelic expression pattern of the non-coding GC-elements flanking chromosomal internal var genes, and transcript from the active one was required for activation of the var gene in the same array. 

Not Open Access | Malaria parasites, immune challenge, MHC variability, and predator avoidance in a passerine bird

September 15, 2015 - 15:57 -- NOT Open Access
Author(s): 
László Zsolt Garamszegi, Magdalena Zagalska-Neubauer, David Canal, Gábor Markó, Eszter Szász, Sándor Zsebők, Eszter Szöllősi, Gábor Herczeg and János Török
Reference: 
Behavioral Ecology (2015) 26 (5): 1292-1302.

This result, in concordance with the above negative results, supports the “avoidance” hypothesis that states that only individuals with efficient immune defense machinery are able to bear the costs of risk-taking that can emerge through the increased infection rates of risk-taker individuals.

Not Open Access | Prevalence of mutations in the antifolates resistance-associated genes (dhfr and dhps) in Plasmodium vivax parasites from Eastern and Central Sudan

June 20, 2014 - 17:45 -- NOT Open Access
Author(s): 
Sekineh Pirahmadi, Badawi Abdelbagi Talha, Bakri Y.M. Nour, Sedigheh Zakeri
Reference: 
Infection, Genetics and Evolution, Volume 26, August 2014, Pages 153-159

Therefore, the main objective of the present study was to provide data on the prevalence of molecular markers in two genes (pvdhfr and pvdhps) associated with SP resistance after nine years of AS + SP deployment among P. vivax parasites from Eastern and Central Sudan using PCR-RFLP.

A flow cytometric assay to quantify invasion of red blood cells by rodent Plasmodium parasites in vivo

April 7, 2014 - 17:17 -- Open Access
Author(s): 
Lelliott PM, Lampkin S, McMorran BJ, Foote SJ, Burgio G
Reference: 
Malaria Journal 2014, 13 :100 (17 March 2014)

Assays for analysing parasite invasion in vitro have been developed, but no equivalent assays exist for in vivo studies. This article describes a novel flow cytometric in vivo parasite invasion assay.

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