scholarly journals cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission

2015 ◽  
Vol 11 (5) ◽  
pp. e1004815 ◽  
Author(s):  
Ghania Ramdani ◽  
Bernina Naissant ◽  
Eloise Thompson ◽  
Florence Breil ◽  
Audrey Lorthiois ◽  
...  
Blood ◽  
2016 ◽  
Vol 127 (24) ◽  
pp. e42-e53 ◽  
Author(s):  
Bernina Naissant ◽  
Florian Dupuy ◽  
Yoann Duffier ◽  
Audrey Lorthiois ◽  
Julien Duez ◽  
...  

Key Points P falciparum STEVORs interact with the erythrocyte cytoskeletal ankyrin complex. Infected erythrocyte deformability is regulated by PKA-mediated phosphorylation of STEVOR cytoplasmic domain.


Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. e172-e180 ◽  
Author(s):  
Marta Tibúrcio ◽  
Makhtar Niang ◽  
Guillaume Deplaine ◽  
Sylvie Perrot ◽  
Emmanuel Bischoff ◽  
...  

AbstractAchievement of malaria elimination requires development of novel strategies interfering with parasite transmission, including targeting the parasite sexual stages (gametocytes). The formation of Plasmodium falciparum gametocytes in the human host takes several days during which immature gametocyte-infected erythrocytes (GIEs) sequester in host tissues. Only mature stage GIEs circulate in the peripheral blood, available to uptake by the Anopheles vector. Mechanisms underlying GIE sequestration and release in circulation are virtually unknown. We show here that mature GIEs are more deformable than immature stages using ektacytometry and microsphiltration methods, and that a switch in cellular deformability in the transition from immature to mature gametocytes is accompanied by the deassociation of parasite-derived STEVOR proteins from the infected erythrocyte membrane. We hypothesize that mechanical retention contributes to sequestration of immature GIEs and that regained deformability of mature gametocytes is associated with their release in the bloodstream and ability to circulate. These processes are proposed to play a key role in P falciparum gametocyte development in the host and to represent novel and unconventional targets for interfering with parasite transmission.


Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2590
Author(s):  
David S. Guttery ◽  
Abhinay Ramaprasad ◽  
David J. P. Ferguson ◽  
Mohammad Zeeshan ◽  
Rajan Pandey ◽  
...  

The meiotic recombination 11 protein (MRE11) plays a key role in DNA damage response and maintenance of genome stability. However, little is known about its function during development of the malaria parasite Plasmodium. Here, we present a functional, ultrastructural and transcriptomic analysis of Plasmodium parasites lacking MRE11 during its life cycle in both mammalian and mosquito vector hosts. Genetic disruption of Plasmodium berghei mre11 (PbMRE11) results in significant retardation of oocyst development in the mosquito midgut associated with cytoplasmic and nuclear degeneration, along with concomitant ablation of sporogony and subsequent parasite transmission. Further, absence of PbMRE11 results in significant transcriptional downregulation of genes involved in key interconnected biological processes that are fundamental to all eukaryotic life including ribonucleoprotein biogenesis, spliceosome function and iron–sulfur cluster assembly. Overall, our study provides a comprehensive functional analysis of MRE11′s role in Plasmodium development during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission.


2015 ◽  
Vol 39 (10) ◽  
Author(s):  
Meng-Hsiun Tsai ◽  
Shyr-Shen Yu ◽  
Yung-Kuan Chan ◽  
Chun-Chu Jen

2021 ◽  
Author(s):  
Rabiatou A. Diarra ◽  
Mohamed M. Traore ◽  
Amy M Junnila ◽  
Sekou F. Traore ◽  
Seydou Doumbia ◽  
...  

Abstract Background Attractive Toxic Sugar Baits (ATSBs) successfully reduced Anopheles mosquito vector populations and malaria parasite transmission in Mali, but application methods need to be improved for wide-scale use, and effects on non-target organisms (NTOs) must be assessed. The goals of this study were to determine on a village level the effect of different outdoor configurations of ATSB bait stations to 1) achieve > 25% Anopheles mosquito vector daily feeding rate for both males and females and 2) minimize the effect on non-target organisms. Methods Dye was added to Attractive Sugar Bait Stations (ASB – without toxin) to mark mosquitoes feeding on the sugar baits, and CDC UV light traps were used to monitor mosquitoes for the presence of the dye. Yellow plates, pitfall traps, Malaise traps, UV light traps, UV tray traps, and sweep nets were used to trap and sample non-target organisms (NTOs) for dye, indicating feeding on the ASB. ASB stations were hung on outer walls of village homes to determine the impact of different densities of ASBs (1,2, or 3 per home) as well as the impact of ASB height (1 m or 1.8 m above the ground on sugar feeding by anophelines. These experiments were carried out separately, on consecutive nights for mosquito and NTO monitoring. Eight villages in the Koulikoro province were chosen as the experimental locations. Results The use of one ASB station per house marked 23.11% of female and 7.11% of male An. gambiae s.l. While two and three ASB stations per house gave feeding rates above the 25% goal, there was no statistical difference in the percentage of marked mosquitoes (p=0.3141 females; p=0.9336 males). There was no difference in sugar feeding on ASB stations when hung at 1.0 and 1.8 m and (p=0.5170 females; p=0.9934 males); however, ASBs at 1.8 m had less accidental damage from village residents and animals, and subsequent invasion of non-targets through rips or holes produced. ASB stations at 1.8 m above ground were fed on by three of seven monitored insect orders. Feeding rates were less than 0.015% of total trap catches and as low as 0.0001%. The monitored orders were: Hymenoptera [ants (Formicidae), bees (Apidae), and wasps (Vespidae)], Lepidoptera (Rhopalocera, Bombyces, Geometroidea, Noctuoidea, Sphingidae, Pyraloidea), Coleoptera (Carabidae, Tenebrionidae, Scarabaeidae, Cerambycidae, and Chrysomelidae), Diptera (Brachycera, Chironomidae), Hemiptera (Cicadomorpha and Heteroptera), Neuroptera (Myrmeleontiformia) and Orthoptera (Caelifera and Ensifera). Using one or two stations limited evidence of NTO feeding to ants (Hymenoptera), Brachycera, Heteroptera, Noctuiodea, Rhopalocera, wasps (Vespidae) and wild bees (Apidae) (both Hymenoptera) and had a significantly reduced percentage of stained individuals compared to three stations which had the highest feeding rates amongst NTOs. The percentages of stained individuals were as follows: 6.84 ± 2.03% Brachycera were stained followed by wasps (Hymenoptera: Vespidae) 5.32 ± 2.27%, and Rhopalocera 2.22 ± 1.79%. Hanging the optimal number of stations per house for catching mosquitoes (two) 1.8 m above ground, limited the groups of non-targets to Brachycera, Chironomidae, Noctuoidea, Rhopalocera, parasitic wasps and wasps (both Hymenoptera: Vespidae). The three most commonly stained non-target insect groups at this height were wasps (Vespidae) (1.65 ± 0.75%), Chironomidae (0.99 ± 0.37), and Brachycera (1.55 ± 0.69%). Feeding at this height only occurred when stations were damaged.Conclusions The goal of marking one quarter of the total Anopheles mosquito vector population per day was obtained using 2 bait stations at 1.8 m height above the ground on the outer walls of houses. This configuration of ATSB stations also had minimal effects on non-target insects: only 0.0001% to 0.013% of specimens (in three orders) were marked. Stations hung 1.8 m above the ground had less accidental damage from passing people and livestock. The minimal marking of non-target insects may be attributed to visual orientation of non-mosquito insects while mosquitoes, are mostly guided by olfactory cues. Furthermore, the bait stations have a membrane cover, which if intact, is impenetrable to most sugar feeding non-target insects but is pierced by the stylets of the mosquito proboscis. Thus, most non-target insects are not exposed to the toxin even if they approach the bait stations.


mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Viswanathan Lakshmanan ◽  
Matthew E. Fishbaugher ◽  
Bob Morrison ◽  
Michael Baldwin ◽  
Michael Macarulay ◽  
...  

ABSTRACT Transmission of malaria occurs during Anopheles mosquito vector blood meals, when Plasmodium sporozoites that have invaded the mosquito salivary glands are delivered to the mammalian host. Sporozoites display a unique form of motility that is essential for their movement across cellular host barriers and invasion of hepatocytes. While the molecular machinery powering motility and invasion is increasingly well defined, the signaling events that control these essential parasite activities have not been clearly delineated. Here, we identify a phosphodiesterase (PDEγ) in Plasmodium, a regulator of signaling through cyclic nucleotide second messengers. Reverse transcriptase PCR (RT-PCR) analysis and epitope tagging of endogenous PDEγ detected its expression in blood stages and sporozoites of Plasmodium yoelii. Deletion of PDEγ (pdeγ−) rendered sporozoites nonmotile, and they failed to invade the mosquito salivary glands. Consequently, PDEγ deletion completely blocked parasite transmission by mosquito bite. Strikingly, pdeγ− sporozoites showed dramatically elevated levels of cyclic GMP (cGMP), indicating that a perturbation in cyclic nucleotide balance is involved in the observed phenotypic defects. Transcriptome sequencing (RNA-Seq) analysis of pdeγ− sporozoites revealed reduced transcript abundance of genes that encode key components of the motility and invasion apparatus. Our data reveal a crucial role for PDEγ in maintaining the cyclic nucleotide balance in the malaria parasite sporozoite stage, which in turn is essential for parasite transmission from mosquito to mammal. IMPORTANCE Malaria is a formidable threat to human health worldwide, and there is an urgent need to identify novel drug targets for this parasitic disease. The parasite is transmitted by mosquito bite, inoculating the host with infectious sporozoite stages. We show that cellular signaling by cyclic nucleotides is critical for transmission of the parasite from the mosquito vector to the mammalian host. Parasite phosphodiesterase γ is essential for maintaining cyclic nucleotide balance, and its deletion blocks transmission of sporozoites. A deeper understanding of the signaling mechanisms involved in transmission might inform the discovery of novel drugs that interrupt this essential step in the parasite life cycle.


2020 ◽  
Vol 28 (24) ◽  
pp. 115832
Author(s):  
Nubia Boechat ◽  
Rita C.C. Carvalho ◽  
Maria de Lourdes G. Ferreira ◽  
Julia Penna Coutinho ◽  
Paula M. Sa ◽  
...  

2016 ◽  
Vol 15 (10) ◽  
pp. 3243-3255 ◽  
Author(s):  
Pablo Suárez-Cortés ◽  
Vikram Sharma ◽  
Lucia Bertuccini ◽  
Giulia Costa ◽  
Naa-Lamiley Bannerman ◽  
...  

2016 ◽  
Vol 113 (26) ◽  
pp. 7183-7188 ◽  
Author(s):  
Jorge M. Santos ◽  
Neuza Duarte ◽  
Jessica Kehrer ◽  
Jai Ramesar ◽  
M. Cristina Avramut ◽  
...  

Transmission of the malaria parasite from the mammalian host to the mosquito vector requires the formation of adequately adapted parasite forms and stage-specific organelles. Here we show that formation of the crystalloid—a unique and short-lived organelle of the Plasmodium ookinete and oocyst stage required for sporogony—is dependent on the precisely timed expression of the S-acyl-transferase DHHC10. DHHC10, translationally repressed in female Plasmodium berghei gametocytes, is activated translationally during ookinete formation, where the protein is essential for the formation of the crystalloid, the correct targeting of crystalloid-resident protein LAP2, and malaria parasite transmission.


2007 ◽  
Vol 76 (6) ◽  
pp. 1072-1078 ◽  
Author(s):  
NIJOLE JASINSKIENE ◽  
AURORA ASHIKYAN ◽  
OSVALDO MARINOTTI ◽  
MICHAEL SALAMPESSY ◽  
JUDY COLEMAN ◽  
...  

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