M3i

@article{Klug2023,

title = {The salivary protein Saglin facilitates efficient midgut colonization of Anopheles mosquitoes by malaria parasites},

author = {Dennis Klug and Amandine Gautier and Eric Calvo and Eric Marois and Stéphanie A. Blandin},

url = {https://doi.org/10.1371/journal.ppat.1010538},

doi = {10.1371/journal.ppat.1010538},

year  = {2023},

date = {2023-03-02},

urldate = {2023-03-02},

booktitle = {Plos Pathogens},

journal = {Plos Pathogens},

volume = {19},

number = {3},

issue = {3},

abstract = {Female mosquitoes rely on blood feeding to acquire sufficient nutrients for egg development. Because of the importance of this process mosquitoes evolved salivary proteins with a broad range of functions acting as blood thinners, anti-coagulants and immunosuppressants. The effect of these proteins on the blood at the bite site directly influences the size of the blood bolus a female takes up in a given time frame. Both, time of feeding and bolus size, are important parameters for fecundity and survival. Recent studies have shown that a significant proportion of salivated proteins is re-ingested during feeding and becomes part of the blood meal. Here we investigated the salivary protein Saglin which has been previously suggested as putative receptor mediating malaria parasite entry into the salivary gland. By engineering a loss-of-function mutant in An. coluzzi we could show that the absence of Saglin impairs the development of parasite stages in the blood meal of the rodent malaria parasite P. berghei and the human malaria parasite P. falciparum lowering the parasite burden of subsequent stages and preventing efficient transmission at low infection densities. Furthermore, we could show that Saglin is present in the blood meal after feeding possibly indicating a previously overlooked parasite-vector interaction.},

keywords = {blandin, BLOOD, M3i, malarial parasites, marois, mosquitoes, Oocysts, Parasitic Diseases, Plasmodium, salivary glands, sporozoites},

pubstate = {published},

tppubtype = {article}

}

@article{volohonsky_plasmodium_2020,

title = {Kinetics of Plasmodium midgut invasion in Anopheles mosquitoes},

author = {Gloria Volohonsky and Perrine Paul-Gilloteaux and Jitka Stafkova and Julien Soichot and Jean Salamero and Elena A. Levashina

},

editor = {Kenneth D. Vernick, Institut Pasteur, FRANCE},

url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008739},

doi = {10.1371/journal.ppat.1008739},

issn = {1553-7374},

year  = {2020},

date = {2020-09-18},

journal = {PLoS Pathog},

volume = {16},

number = {9},

abstract = {The traversal of the mosquito midgut cells is one of the critical stages in the life cycle of malaria parasites. Motile parasite forms, called ookinetes, traverse the midgut epithelium in a dynamic process which is not fully understood. Here, we harnessed transgenic reporters to track invasion of Plasmodium parasites in African and Indian mosquito species. We found important differences in parasite dynam- ics between the two Anopheles species and demonstrated a role of the mosquito comple- ment-like system in regulation of parasite invasion of the midgut cells.},

keywords = {Anopheles, M3i, Malaria, marois, midgut, Plasmodium},

pubstate = {published},

tppubtype = {article}

}

@article{ehrhardt_redox-cycler_2016,

title = {The redox-cycler plasmodione is a fast acting antimalarial lead compound with pronounced activity against sexual and early asexual blood-stage parasites},

author = {Katharina Ehrhardt and Christiane Deregnaucourt and Alice-Anne Goetz and Tzvetomira Tzanova and Valentina Gallo and Paolo Arese and Bruno Pradines and Sophie H Adjalley and Denyse Bagrel and Stephanie A Blandin and Michael Lanzer and Elisabeth Davioud-Charvet},

url = {http://aac.asm.org/content/60/9/5146},

doi = {10.1128/AAC.02975-15},

issn = {1098-6596},

year  = {2016},

date = {2016-09-01},

journal = {Antimicrob. Agents Chemother.},

volume = {60},

number = {9},

pages = {5146-5158},

abstract = {Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent in vitro and in vivo activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox-cyclers - a strategy that is broadly recognized for the development of new antimalarial agents. Here, we report a detailed parasitological characterization of the in vitro activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intra-erythrocytic stages of the human malaria parasite Plasmodium falciparum We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intra-erythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common resistance mechanisms to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a fast killing speed as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that it is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents.},

keywords = {antimalarial, blandin, M3i, parasites, Plasmodium, redox-cycler},

pubstate = {published},

tppubtype = {article}

}

@article{fraiture_two_2009,

title = {Two mosquito LRR proteins function as complement control factors in the TEP1-mediated killing of Plasmodium},

author = {Malou Fraiture and Richard H G Baxter and Stefanie Steinert and Yogarany Chelliah and Cécile Frolet and Wilber Quispe-Tintaya and Jules A Hoffmann and Stéphanie A Blandin and Elena A Levashina},

doi = {10.1016/j.chom.2009.01.005},

issn = {1934-6069},

year  = {2009},

date = {2009-03-01},

journal = {Cell Host Microbe},

volume = {5},

number = {3},

pages = {273--284},

abstract = {Plasmodium development within Anopheles mosquitoes is a vulnerable step in the parasite transmission cycle, and targeting this step represents a promising strategy for malaria control. The thioester-containing complement-like protein TEP1 and two leucine-rich repeat (LRR) proteins, LRIM1 and APL1, have been identified as major mosquito factors that regulate parasite loads. Here, we show that LRIM1 and APL1 are required for binding of TEP1 to parasites. RNAi silencing of the LRR-encoding genes results in deposition of TEP1 on Anopheles tissues, thereby depleting TEP1 from circulation in the hemolymph and impeding its binding to Plasmodium. LRIM1 and APL1 not only stabilize circulating TEP1, they also stabilize each other prior to their interaction with TEP1. Our results indicate that three major antiparasitic factors in mosquitoes jointly function as a complement-like system in parasite killing, and they reveal a role for LRR proteins as complement control factors.},

keywords = {Animals, Anopheles, APL1, Biological, blandin, Complement System Proteins, Hemolymph, hoffmann, Immunologic Factors, LRIM1, M3i, Models, Plasmodium, Protein Binding, Proteins, TEP1},

pubstate = {published},

tppubtype = {article}

}

@article{blandin_mosquito_2004,

title = {Mosquito immune responses against malaria parasites},

author = {Stéphanie A Blandin and Elena A Levashina},

issn = {0952-7915},

year  = {2004},

date = {2004-01-01},

journal = {Curr. Opin. Immunol.},

volume = {16},

number = {1},

pages = {16--20},

abstract = {Anopheline mosquitoes are the major vectors of human malaria. Mosquito-parasite interactions are a critical aspect of disease transmission and a potential target for malaria control. Mosquitoes vary in their innate ability to support development of the malaria parasite, but the molecular mechanisms that determine vector competence are poorly understood. This area of research has been revolutionized by recent advances in the mosquito genome characterization and by the development of new tools for functional gene analysis.},

keywords = {Animals, Anopheles, blandin, Gene Library, Genes, Hemocytes, Host-Parasite Interactions, Immunity, Innate, Insect, Insect Vectors, M3i, Malaria, Plasmodium},

pubstate = {published},

tppubtype = {article}

}

@article{christophides_immunity-related_2002,

title = {Immunity-related genes and gene families in Anopheles gambiae},

author = {George K Christophides and Evgeny Zdobnov and Carolina Barillas-Mury and Ewan Birney and Stephanie A Blandin and Claudia Blass and Paul T Brey and Frank H Collins and Alberto Danielli and George Dimopoulos and Charles Hetru and Ngo T Hoa and Jules A Hoffmann and Stefan M Kanzok and Ivica Letunic and Elena A Levashina and Thanasis G Loukeris and Gareth Lycett and Stephan Meister and Kristin Michel and Luis F Moita and Hans-Michael Müller and Mike A Osta and Susan M Paskewitz and Jean-Marc Reichhart and Andrey Rzhetsky and Laurent Troxler and Kenneth D Vernick and Dina Vlachou and Jennifer Volz and Christian von Mering and Jiannong Xu and Liangbiao Zheng and Peer Bork and Fotis C Kafatos},

url = {http://www.ncbi.nlm.nih.gov/pubmed/12364793},

doi = {10.1126/science.1077136},

issn = {1095-9203},

year  = {2002},

date = {2002-10-01},

journal = {Science},

volume = {298},

number = {5591},

pages = {159--165},

abstract = {We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire.},

keywords = {Alternative Splicing, Animals, Anopheles, Apoptosis, bacteria, bioinformatic, blandin, Catechol Oxidase, Computational Biology, Enzyme Precursors, Gene Expression Regulation, Genes, Genetic, Genome, hoffmann, Immunity, Innate, Insect, Insect Proteins, M3i, Multigene Family, Peptides, Phylogeny, Plasmodium, Protein Structure, reichhart, Selection, Serine Endopeptidases, Serpins, Signal Transduction, Tertiary},

pubstate = {published},

tppubtype = {article}

}

@article{lowenberger_mosquito-plasmodium_1999,

title = {Mosquito-Plasmodium interactions in response to immune activation of the vector},

author = {C A Lowenberger and S Kamal and J Chiles and S Paskewitz and Philippe Bulet and Jules A Hoffmann and B M Christensen},

doi = {10.1006/expr.1999.4350},

issn = {0014-4894},

year  = {1999},

date = {1999-01-01},

journal = {Exp. Parasitol.},

volume = {91},

number = {1},

pages = {59--69},

abstract = {During the development of Plasmodium sp. within the mosquito midgut, the parasite undergoes a series of developmental changes. The elongated ookinete migrates through the layers of the midgut where it forms the oocyst under the basal lamina. We demonstrate here that if Aedes aegypti or Anopheles gambiae, normally susceptible to Plasmodium gallinaceum and P. berghei, respectively, are immune activated by the injection of bacteria into the hemocoel, and subsequently are fed on an infectious bloodmeal, there is a significant reduction in the prevalence and mean intensity of infection of oocysts on the midgut. Only those mosquitoes immune activated prior to, or immediately after, parasite ingestion exhibit this reduction in parasite development. Mosquitoes immune activated 2-5 days after bloodfeeding show no differences in parasite burdens compared with naive controls. Northern analyses reveal that transcriptional activity for mosquito defensins is not detected in the whole bodies of Ae. aegypti from 4 h to 10 days after ingesting P. gallinaceum, suggesting that parasite ingestion, passage from the food bolus through the midgut, oocyst formation, and subsequent release of sporozoites into the hemolymph do not induce the production of defensin. However, reverse transcriptase-PCR of RNA isolated solely from the midguts of Ae. aegypti indicates that transcription of mosquito defensins occurs in the midguts of naive mosquitoes and those ingesting an infectious or noninfectious bloodmeal. Bacteria-challenged Ae. aegypti showed high levels of mature defensin in the hemolymph that correlate with a lower prevalence and mean intensity of infection with oocysts. Because few oocysts were found on the midgut of immune-activated mosquitoes, the data suggest that some factor, induced by bacterial challenge, kills the parasite at a preoocyst stage.},

keywords = {Aedes, Animals, Anopheles, Culicidae, Defensins, Digestive System, Escherichia coli, Female, Genetic, Hemolymph, hoffmann, Insect Vectors, M3i, messenger, Micrococcus luteus, Plasmodium, Plasmodium berghei, Plasmodium gallinaceum, Proteins, Reverse Transcriptase Polymerase Chain Reaction, RNA, Transcription},

pubstate = {published},

tppubtype = {article}

}

@article{hoffmann_immune_1997,

title = {Immune responsiveness in vector insects},

author = {Jules A Hoffmann},

issn = {0027-8424},

year  = {1997},

date = {1997-10-01},

journal = {Proc. Natl. Acad. Sci. U.S.A.},

volume = {94},

number = {21},

pages = {11152--11153},

keywords = {Animals, Anopheles, bacteria, Blood Proteins, Defensins, hoffmann, Humans, Insect Vectors, Life Cycle Stages, M3i, Malaria, Mammals, Plasmodium},

pubstate = {published},

tppubtype = {article}

}