scholarly journals Inhibitors of Eicosanoid Biosynthesis Reveal that Multiple Lipid Signaling Pathways Influence Malaria Parasite Survival in Anopheles gambiae

Insects ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 307 ◽  
Author(s):  
Kwon ◽  
Smith
Keyword(s):  
Fatty Acids ◽  
Anopheles Gambiae ◽  
Malaria Parasite ◽  
Parasite Infection ◽  
Immune Homeostasis ◽  
Dodecanoic Acid ◽  
Parasite Survival ◽  
Mosquito Anopheles Gambiae ◽  
Inflammatory Drugs ◽  
Specific Inhibitors

Eicosanoids are bioactive signaling lipids derived from the oxidation of fatty acids that act as important regulators of immune homeostasis and inflammation. As a result, effective anti-inflammatory drugs have been widely used to reduce pain and inflammation which target key eicosanoid biosynthesis enzymes. Conserved from vertebrates to insects, the use of these eicosanoid pathway inhibitors offer opportunities to evaluate the roles of eicosanoids in less-characterized insect systems. In this study, we examine the potential roles of eicosanoids on malaria parasite survival in the mosquito Anopheles gambiae. Using Plasmodium oocyst numbers to evaluate parasite infection, general or specific inhibitors of eicosanoid biosynthesis pathways were evaluated. Following the administration of dexamethasone and indomethacin, respective inhibitors of phospholipid A2 (PLA2) and cyclooxygenase (COX), oocyst numbers were unaffected. However, inhibition of lipoxygenase (LOX) activity through the use of esculetin significantly increased oocyst survival. In contrast, 12-[[(tricyclo[3.3.1.13,7]dec-1-ylamino)carbonyl]amino]-dodecanoic acid (AUDA), an inhibitor of epoxide hydroxylase (EH), decreased oocyst numbers. These experiments were further validated through RNAi experiments to silence candidate genes homologous to EH in An. gambiae to confirm their contributions to Plasmodium development. Similar to the results of AUDA treatment, the silencing of EH significantly reduced oocyst numbers. These results imply that specific eicosanoids in An. gambiae can have either agonist or antagonistic roles on malaria parasite survival in the mosquito host.

scholarly journals microRNA tissue atlas of the malaria mosquito Anopheles gambiae

2017 ◽  
Author(s):  
Lena Lampe ◽  
Elena A. Levashina
Keyword(s):  
Plasmodium Falciparum ◽  
Anopheles Gambiae ◽  
Mirna Expression ◽  
Blood Meal ◽  
Life Style ◽  
Malaria Parasite ◽  
Malaria Mosquito ◽  
Human Malaria Parasite ◽  
Mosquito Anopheles Gambiae ◽  
Blood Meal Digestion

ABSTRACTAnopheles gambiae mosquitoes transmit the human malaria parasite Plasmodium falciparum, which causes the majority of fatal malaria cases worldwide. The hematophagous life style defines the mosquito reproductive biology and is exploited by P. falciparum for its own sexual reproduction and transmission. The two main phases of the mosquito reproductive cycle, pre-vitellogenic (PV) and post-blood meal (PBM) shape its capacity to transmit malaria. Transition between these phases is tightly coordinated to ensure homeostasis between mosquito tissues and successful reproduction. One layer of control is provided by microRNAs, well known regulators of blood meal digestion and egg development in Aedes mosquitoes. Here, we report a global overview of tissue-specific miRNA expression during the PV and PBM phases and identify miRNAs regulated during PV to PBM transition. The observed coordinated changes in the expression levels of a set of miRNAs in the energy-storing tissues suggest a role in the regulation of blood meal-induced metabolic changes.

scholarly journals A malaria parasite phospholipid flippase safeguards midgut traversal of ookinetes for mosquito transmission

2021 ◽  
Author(s):  
Zhenke Yang ◽  
Yang Shi ◽  
Huiting Cui ◽  
Shuzhen Yang ◽  
Han Gao ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Bilayers ◽  
Malaria Parasite ◽  
Parasite Infection ◽  
Midgut Epithelium ◽  
Rodent Malaria Parasite ◽  
Membrane Asymmetry ◽  
Type Iv ◽  
Parasite Survival ◽  
Phospholipid Flippase

Mosquito midgut epithelium traversal is an essential component of transmission of malaria parasites. Phospholipid flippases are eukaryotic type IV ATPases (P4-ATPases), which in association with CDC50 cofactors, translocate phospholipids across lipid bilayers to maintain the membrane asymmetry. In this study, we investigated the function of a putative P4-ATPase, ATP7, from the rodent malaria parasite P. yoelii. Disruption of ATP7 results in block of parasite infection of mosquitoes. ATP7 is localized on the ookinete plasma membrane. While ATP7-depleted ookinetes are motile and capable of invading the midgut, they are quickly eliminated within the epithelial cells by a process that is independent from the mosquito complement-like immunity. ATP7 colocalizes and interacts with the flippase co-factor CDC50C. Importantly, depletion of CDC50C phenocopies ATP7 deficiency. ATP7-depleted ookinetes fail to translocate phosphatidylcholine (PC) across the plasma membrane, resulting in PC exposure at the ookinete surface. Lastly, ookinete microinjection into the mosquito hemocoel reverses the ATP7 deficiency phenotype. Our study identifies Plasmodium flippase as a novel mechanism of parasite survival in the midgut epithelium that is required for mosquito transmission.

scholarly journals Chemical depletion of phagocytic immune cells reveals dual roles of mosquito hemocytes in Anopheles gambiae anti-Plasmodium immunity

2018 ◽  
Author(s):  
Hyeogsun Kwon ◽  
Ryan C. Smith
Keyword(s):  
Immune Responses ◽  
Anopheles Gambiae ◽  
Immune Cells ◽  
Malaria Parasite ◽  
Morphological Characteristics ◽  
Invertebrate Immunity ◽  
Dual Roles ◽  
Humoral Factors ◽  
Parasite Survival ◽  
First Time

AbstractMosquito innate immunity is comprised of both cellular and humoral factors that provide protection from invading pathogens. Immune cells, known as hemocytes, have been intricately associated with these immune responses through direct roles in phagocytosis and immune signaling. Recent studies have implicated hemocytes as integral determinants of anti-Plasmodium immunity, yet little is known regarding the specific mechanisms by which hemocytes limit malaria parasite survival. With limited genetic tools to enable their study, we employed a chemical-based treatment widely used for macrophage depletion in mammalian systems for the first time in an invertebrate organism. Upon its application in Anopheles gambiae, we observe distinct populations of phagocytic immune cells that are significantly depleted, causing high mortality following bacterial challenge and an increased intensity of malaria parasite infection. Through these studies, we demonstrate that phagocytes are required for mosquito complement recognition of invading ookinetes, as well as the production of prophenoloxidases that limit oocyst survival. Through these experiments, we also define specific sub-types of phagocytic immune cells in An. gambiae, providing new insights beyond the morphological characteristics that traditionally define mosquito hemocyte populations. Together, this study provides the first definitive insights into the dual roles of mosquito phagocytes in limiting malaria parasite survival, and illustrates the use of clodronate liposomes as an important advancement in the study of invertebrate immunity.

scholarly journals CRISPR/Cas9 -mediated gene knockout of Anopheles gambiae FREP1 suppresses malaria parasite infection

2018 ◽  
Vol 14 (3) ◽  
pp. e1006898 ◽  
Author(s):  
Yuemei Dong ◽  
Maria L. Simões ◽  
Eric Marois ◽  
George Dimopoulos
Keyword(s):  
Anopheles Gambiae ◽  
Malaria Parasite ◽  
Gene Knockout ◽  
Parasite Infection ◽  
Malaria Parasite Infection

scholarly journals Toxoplasma LIPIN is essential in channeling host lipid fluxes through membrane biogenesis and lipid storage

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sheena Dass ◽  
Serena Shunmugam ◽  
Laurence Berry ◽  
Christophe-Sebastien Arnold ◽  
Nicholas J. Katris ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Phosphatidic Acid ◽  
De Novo ◽  
Lipid Synthesis ◽  
Parasite Development ◽  
Membrane Biogenesis ◽  
Membrane Phospholipids ◽  
Phosphatidic Acid Phosphatase ◽  
Intracellular Parasites ◽  
Parasite Survival

AbstractApicomplexa are obligate intracellular parasites responsible for major human diseases. Their intracellular survival relies on intense lipid synthesis, which fuels membrane biogenesis. Parasite lipids are generated as an essential combination of fatty acids scavenged from the host and de novo synthesized within the parasite apicoplast. The molecular and metabolic mechanisms allowing regulation and channeling of these fatty acid fluxes for intracellular parasite survival are currently unknown. Here, we identify an essential phosphatidic acid phosphatase in Toxoplasma gondii, TgLIPIN, as the central metabolic nexus responsible for controlled lipid synthesis sustaining parasite development. Lipidomics reveal that TgLIPIN controls the synthesis of diacylglycerol and levels of phosphatidic acid that regulates the fine balance of lipids between storage and membrane biogenesis. Using fluxomic approaches, we uncover the first parasite host-scavenged lipidome and show that TgLIPIN prevents parasite death by ‘lipotoxicity’ through effective channeling of host-scavenged fatty acids to storage triacylglycerols and membrane phospholipids.

scholarly journals Low-resolution genome map of the malaria mosquito Anopheles gambiae.

1991 ◽  
Vol 88 (24) ◽  
pp. 11187-11191 ◽  
Author(s):  
L. B. Zheng ◽  
R. D. Saunders ◽  
D. Fortini ◽  
A. della Torre ◽  
M. Coluzzi ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Malaria Mosquito ◽  
Low Resolution ◽  
Genome Map ◽  
Mosquito Anopheles Gambiae
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