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blood stage

NOT Open Access | The endoplasmic reticulum-resident serpentine receptor SR10 has important functions for asexual and sexual blood stage development of Plasmodium falciparum

September 15, 2020 - 15:09 -- NOT Open Access
Author(s): 
Njila Tchoufack EJ, Hahnfeld L, Pitschelatow G, Bennink S, Pradel G
Reference: 
Mol Biochem Parasitol. 2020 Sep 2:111315

Serpentine receptors (SRs) are transmembrane proteins generally acting as mediators to facilitate the communication between a cell and its environment. At least six putative SR-like proteins are encoded in the genome of the malaria parasite Plasmodium falciparum.

Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage

September 15, 2020 - 10:59 -- Open Access
Author(s): 
Hojo-Souza NS, de Azevedo PO, de Castro JT, Teixeira-Carvalho A, Lieberman J, Junqueira C, Gazzinelli RT
Reference: 
PLoS Pathog. 2020 Sep 10;16(9):e1008840

P. vivax-infected Retics (iRetics) express human leukocyte antigen class I (HLA-I), are recognized by CD8+ T cells and killed by granulysin (GNLY) and granzymes. However, how Plasmodium infection induces MHC-I expression on Retics is unknown. In addition, whether GNLY helps control Plasmodium infection in vivo has not been studied. Here, we examine these questions using rodent infection with the P. yoelii 17XNL strain, which has tropism for Retics.

NOT Open Access | Dynamics of blood stage and sporozoite-induced malarial infections in experimentally infected passerines

September 8, 2020 - 11:44 -- NOT Open Access
Author(s): 
Palinauskas V, Platonova E, Žiegytė R, Mukhin A
Reference: 
Int J Parasitol. 2020 Aug 31:S0020-7519(20)30248-4

Complex experimental studies of vertebrate host, vector, and parasite interactions are essential in understanding virulence, but are difficult or impossible to conduct if vector species are unknown. Subinoculation of erythrocytic meronts of avian malarial parasites into susceptible hosts can avoid this problem, but this approach omits early exoerythrocytic stages, e.g. cryptozoites and metacryptozoites, that normally develop from sporozoites.

Inhibition of Resistance-Refractory P. falciparum Kinase PKG Delivers Prophylactic, Blood Stage, and Transmission-Blocking Antiplasmodial Activity

July 21, 2020 - 12:14 -- Open Access
Author(s): 
Vanaerschot M, Murithi JM, Fidock DA, et al.
Reference: 
Cell Chem Biol. 2020 Jul 16; 27(7):806-816.e8

The search for antimalarial chemotypes with modes of action unrelated to existing drugs has intensified with the recent failure of first-line therapies across Southeast Asia. Here, we show that the trisubstituted imidazole MMV030084 potently inhibits hepatocyte invasion by Plasmodium sporozoites, merozoite egress from asexual blood stage schizonts, and male gamete exflagellation.

A genetically hmgb2 attenuated blood stage P. berghei induces crossed-long live protection

May 12, 2020 - 16:47 -- Open Access
Author(s): 
Briquet S, Lawson-Hogban N, Peronet R, Mécheri S, Vaquero C
Reference: 
PLoS ONE 15(5): e0232183

Due to the lack of efficiency to control malaria elicited by sub-unit vaccine preparations, vaccination with live-attenuated Plasmodium parasite as reported 70 years ago with irradiated sporozoites regained recently a significant interest. The complex life cycle of the parasite and the different stages of development between mammal host and anopheles do not help to propose an easy vaccine strategy.

Maintaining immunogenicity of blood stage and sexual stage subunit malaria vaccines when formulated in combination

May 4, 2020 - 14:04 -- Open Access
Author(s): 
Parzych EM, Miura K, Long CA, Burns JM Jr
Reference: 
PLoS ONE 15(4): e0232355

Eradication of Plasmodium falciparum malaria will likely require a multivalent vaccine, but the development of a highly efficacious subunit-based formulation has been challenging. We previously showed that production and immunogenicity of two leading vaccine targets, PfMSP119 (blood-stage) and Pfs25 (sexual stage), could be enhanced upon genetic fusion to merozoite surface protein 8 (PfMSP8). Here, we sought to optimize a Pfs25-based formulation for use in combination with rPfMSP1/8 with the goal of maintaining the immunogenicity of each subunit.

Screening the Medicines for Malaria Venture Pathogen Box for invasion and egress inhibitors of the blood stage of Plasmodium falciparum reveals several inhibitory compounds

March 10, 2020 - 16:21 -- Open Access
Author(s): 
Dans MG, Weiss GE, Wilson DW, Sleebs BE, Crabb BS, de Koning-Ward TF, Gilson PR
Reference: 
Int J Parasitol. 2020 Mar 2. pii: S0020-7519(20)30033-3

With emerging resistance to frontline treatments, it is vital that new drugs are identified to target Plasmodium falciparum. One of the most critical processes during the parasites’ asexual lifecycle is the invasion and subsequent egress of red blood cells (RBCs). Many unique parasite ligands, receptors and enzymes are employed during egress and invasion that are essential for parasite proliferation and survival, therefore making these processes druggable targets.

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