scholarly journals Rhoptry neck protein 11 has crucial roles during malaria parasite sporozoite invasion of salivary glands and hepatocytes

2019 ◽  
Vol 49 (9) ◽  
pp. 725-735 ◽  
Author(s):  
Sirasate Bantuchai ◽  
Mamoru Nozaki ◽  
Amporn Thongkukiatkul ◽  
Natcha Lorsuwannarat ◽  
Mayumi Tachibana ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Malaria Parasite ◽  
Rhoptry Neck Protein

scholarly journals Detection of the Rhoptry Neck Protein Complex in Plasmodium Sporozoites and Its Contribution to Sporozoite Invasion of Salivary Glands

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Mamoru Nozaki ◽  
Minami Baba ◽  
Mayumi Tachibana ◽  
Naohito Tokunaga ◽  
Motomi Torii ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Protein Complex ◽  
Malaria Parasite ◽  
Gene Knockdown ◽  
Mammalian Host ◽  
Target Cells ◽  
Specific Gene ◽  
Invasion Mechanisms ◽  
Attachment Ability ◽  
Rhoptry Neck Protein

ABSTRACT In the Plasmodium life cycle, two infectious stages of parasites, merozoites and sporozoites, share rhoptry and microneme apical structures. A crucial step during merozoite invasion of erythrocytes is the discharge to the host cell membrane of some rhoptry neck proteins as a complex, followed by the formation of a moving junction involving the parasite-secreted protein AMA1 on the parasite membrane. Components of the merozoite rhoptry neck protein complex are also expressed in sporozoites, namely, RON2, RON4, and RON5, suggesting that invasion mechanism elements might be conserved between these infective stages. Recently, we demonstrated that RON2 is required for sporozoite invasion of mosquito salivary gland cells and mammalian hepatocytes, using a sporozoite stage-specific gene knockdown strategy in the rodent malaria parasite model, Plasmodium berghei. Here, we use a coimmunoprecipitation assay and oocyst-derived sporozoite extracts to demonstrate that RON2, RON4, and RON5 also form a complex in sporozoites. The sporozoite stage-specific gene knockdown strategy revealed that both RON4 and RON5 have crucial roles during sporozoite invasion of salivary glands, including a significantly reduced attachment ability required for the onset of gliding. Further analyses indicated that RON2 and RON4 reciprocally affect trafficking to rhoptries in developing sporozoites, while RON5 is independently transported. These findings indicate that the interaction between RON2 and RON4 contributes to their stability and trafficking to rhoptries, in addition to involvement in sporozoite attachment. IMPORTANCE Sporozoites are the motile infectious stage that mediates malaria parasite transmission from mosquitoes to the mammalian host. This study addresses the question whether the rhoptry neck protein complex forms and functions in sporozoites, in addition to its role in merozoites. By applying coimmunoprecipitation and sporozoite stage-specific gene knockdown assays, it was demonstrated that RON2, RON4, and RON5 form a complex and are involved in sporozoite invasion of salivary glands via their attachment ability. These findings shed light on the conserved invasion mechanisms among apicomplexan infective stages. In addition, the sporozoite stage-specific gene knockdown system has revealed for the first time in Plasmodium that the RON2 and RON4 interaction reciprocally affects their stability and trafficking to rhoptries. Our study raises the possibility that the RON complex functions during sporozoite maturation as well as migration toward and invasion of target cells.

scholarly journals Cyclic GMP Balance Is Critical for Malaria Parasite Transmission from the Mosquito to the Mammalian Host

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Viswanathan Lakshmanan ◽  
Matthew E. Fishbaugher ◽  
Bob Morrison ◽  
Michael Baldwin ◽  
Michael Macarulay ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Cyclic Gmp ◽  
Cyclic Nucleotide ◽  
Malaria Parasite ◽  
Plasmodium Yoelii ◽  
Pcr Analysis ◽  
Mammalian Host ◽  
Mosquito Vector ◽  
Parasite Transmission ◽  
Mosquito Bite

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.

scholarly journals Salivary Glands Proteins Expression ofAnopheles dirusA Fed onPlasmodium vivax-andPlasmodium falciparum-Infected Human Blood

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Saowanee Cotama ◽  
Paron Dekumyoy ◽  
Yudthana Samung ◽  
Usa Lek-Uthai
Keyword(s):  
Salivary Glands ◽  
Malaria Parasite ◽  
Protein Band ◽  
Normal Blood ◽  
Artificial Membrane ◽  
Parasite Life Cycle ◽  
Infected Blood ◽  
Molecular Weights ◽  
Sds Page ◽  
Mosquito Salivary Gland

Mosquitoes are able to adapt to feed on blood by the salivary glands which created a protein that works against the haemostasis process. This study aims to investigate the salivary glands proteins expression of 50 adult femaleAn. dirusA mosquitoes, a main vector of malaria in Thailand, each group with an age of 5 days which were artificial membrane fed on sugar, normal blood, blood infected withP. vivax, and blood infected withP. falciparum. Then mosquito salivary gland proteins were analyzed by SDS-PAGE on days 0, 1, 2, 3, and 4 after feeding. The findings revealed that the major salivary glands proteins had molecular weights of 62, 58, 43, 36, 33, 30, and 18 kDa. One protein band of approximately 13 kDa was found in normal blood and blood infected withP. vivaxfed on day 0. A stronger protein band, 65 kDa, was expressed from the salivary glands of mosquitoes fed withP. vivax- orP. falciparum-infected blood on only day 0, but none on days 1 to 4. The study shows that salivary glands proteins expression ofAn. dirusmay affect the malaria parasite life cycle and the ability of mosquitoes to transmit malaria parasites in post-24-hour disappearance observation.

scholarly journals Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Scott E. Lindner ◽  
Kristian E. Swearingen ◽  
Melanie J. Shears ◽  
Michael P. Walker ◽  
Erin N. Vrana ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Salivary Gland ◽  
Protein Expression ◽  
Salivary Glands ◽  
Malaria Parasite ◽  
Plasmodium Yoelii ◽  
Translational Repression ◽  
Successful Development ◽  
Regulate Protein ◽  
Validation Experiments

Abstract Plasmodium sporozoites are transmitted from infected mosquitoes to mammals, and must navigate the host skin and vasculature to infect the liver. This journey requires distinct proteomes. Here, we report the dynamic transcriptomes and proteomes of both oocyst sporozoites and salivary gland sporozoites in both rodent-infectious Plasmodium yoelii parasites and human-infectious Plasmodium falciparum parasites. The data robustly define mRNAs and proteins that are upregulated in oocyst sporozoites (UOS) or upregulated in infectious sporozoites (UIS) within the salivary glands, including many that are essential for sporozoite functions in the vector and host. Moreover, we find that malaria parasites use two overlapping, extensive, and independent programs of translational repression across sporozoite maturation to temporally regulate protein expression. Together with gene-specific validation experiments, these data indicate that two waves of translational repression are implemented and relieved at different times during sporozoite maturation, migration and infection, thus promoting their successful development and vector-to-host transition.

scholarly journals Comparison of malaria parasite gametocyte activating factor in the salivary glands of five species of mosquito (Diptera : Culicidae)

2002 ◽  
Vol 53 (3) ◽  
pp. 177-182 ◽  
Author(s):  
Jichun WANG ◽  
Makoto HIRAI ◽  
Shigeto YOSHIDA ◽  
Meiji ARAI ◽  
Akira ISHII ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Malaria Parasite

scholarly journals Distinct Malaria Parasite Sporozoites Reveal Transcriptional Changes That Cause Differential Tissue Infection Competence in the Mosquito Vector and Mammalian Host

2008 ◽  
Vol 28 (20) ◽  
pp. 6196-6207 ◽  
Author(s):  
Sebastian A. Mikolajczak ◽  
Hilda Silva-Rivera ◽  
Xinxia Peng ◽  
Alice S. Tarun ◽  
Nelly Camargo ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Malaria Parasite ◽  
Transmembrane Protein ◽  
Tissue Infection ◽  
Mammalian Host ◽  
Mosquito Vector ◽  
Targeted Gene Deletion ◽  
Transcriptional Changes ◽  
Host Infection ◽  
Genome Scale

ABSTRACT The malaria parasite sporozoite transmission stage develops and differentiates within parasite oocysts on the Anopheles mosquito midgut. Successful inoculation of the parasite into a mammalian host is critically dependent on the sporozoite's ability to first infect the mosquito salivary glands. Remarkable changes in tissue infection competence are observed as the sporozoites transit from the midgut oocysts to the salivary glands. Our microarray analysis shows that compared to oocyst sporozoites, salivary gland sporozoites upregulate expression of at least 124 unique genes. Conversely, oocyst sporozoites show upregulation of at least 47 genes (upregulated in oocyst sporozoites [UOS genes]) before they infect the salivary glands. Targeted gene deletion of UOS3, encoding a putative transmembrane protein with a thrombospondin repeat that localizes to the sporozoite secretory organelles, rendered oocyst sporozoites unable to infect the mosquito salivary glands but maintained the parasites' liver infection competence. This phenotype demonstrates the significance of differential UOS expression. Thus, the UIS-UOS gene classification provides a framework to elucidate the infectivity and transmission success of Plasmodium sporozoites on a whole-genome scale. Genes identified herein might represent targets for vector-based transmission blocking strategies (UOS genes), as well as strategies that prevent mammalian host infection (UIS genes).

scholarly journals Rhoptry neck protein 2 expressed in Plasmodium sporozoites plays a crucial role during invasion of mosquito salivary glands

2018 ◽  
Vol 21 (1) ◽  
pp. e12964 ◽  
Author(s):  
Tomoko Ishino ◽  
Eri Murata ◽  
Naohito Tokunaga ◽  
Minami Baba ◽  
Mayumi Tachibana ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Crucial Role ◽  
Rhoptry Neck Protein

Plasmodium knowlesi and human malaria parasites in Khan Phu, Vietnam: Gametocyte production in humans and frequent co-infection of mosquitoes

Parasitology ◽  
2016 ◽  
Vol 144 (4) ◽  
pp. 527-535 ◽  
Author(s):  
Y. MAENO ◽  
R. CULLETON ◽  
N. T. QUANG ◽  
S. KAWAI ◽  
R. P. MARCHAND ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Malaria Parasite ◽  
Plasmodium Knowlesi ◽  
Plasmodium Malariae ◽  
Transmission Dynamics ◽  
Malaria Parasites ◽  
Macaque Monkeys ◽  
Human Malaria ◽  
Human Infections ◽  
Specific Mrna

SUMMARYFour species of malaria parasite, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium knowlesi infect humans living in the Khanh Phu commune, Khanh Hoa Province, Vietnam. The latter species also infects wild macaque monkeys in this region. In order to understand the transmission dynamics of the three species, we attempted to detect gametocytes of the three species in the blood of infected individuals, and sporozoites in the salivary glands of mosquitoes from the same region. For the detection of gametocyte-specific mRNA, we targeted region 3 of pfg377, pvs25, pmg and pks25 as indicators of the presence of P. falciparum, P. vivax, P. malariae and P. knowlesi gametocytes, respectively. Gametocyte-specific mRNA was present in 37, 61, 0 and 47% of people infected with P. falciparum (n = 95), P. vivax (n = 69), P. malariae (n = 6) or P. knowlesi (n = 32), respectively. We found that 70% of mosquitoes that had P. knowlesi in their salivary glands also carried human malaria parasites, suggesting that mosquitoes are infected with P. knowlesi from human infections.

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