Novel salivary antihemostatic activities of long-form D7 proteins from the malaria vector Anopheles gambiae facilitate hematophagy

Smith, Leticia Barion; Duge, Emma; Valenzuela-León, Paola Carolina; Brooks, Steven; Martín-Martín, Inés; Ackerman, Hans; Calvo, Eric

doi:10.1016/j.jbc.2022.101971

Cited by 8 publications

(4 citation statements)

References 42 publications

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“…The functions of An. gambiae D7 long forms (AngaD7L1, L2, and L3) were recently discovered ( Smith et al, 2022 ). AngaD7L1 binds leukotriene C4 and thromboxane A2 analog U-46619 while AngaD7L2 weakly binds leukotrienes B4 and D4.…”

Section: Resultsmentioning

confidence: 99%

A deeper insight into the sialome of male and female Ochlerotatus triseriatus mosquitoes

Martín-Martín

Ribeiro

et al. 2022

Insect Biochemistry and Molecular Biology

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Section: Resultsmentioning

confidence: 99%

A deeper insight into the sialome of male and female Ochlerotatus triseriatus mosquitoes

Martín-Martín

Ribeiro

et al. 2022

Insect Biochemistry and Molecular Biology

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“…Over the last decade several members of the D7 protein family have been functionally and structurally characterized and shown to act as kratagonists , proteins capable of binding and trapping small agonists relevant for host homeostasis such as biogenic amines and leukotrienes [ 36 – 40 ]. Recently, two long-D7 from C. quinquefasciatus were described as kratagonists [ 10 ].…”

Section: Resultsmentioning

confidence: 99%

A deeper insight into the sialome of male and female Culex quinquefasciatus mosquitoes

Martín-Martín

Ribeiro

et al. 2023

BMC Genomics

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Introduction During evolution, blood-feeding arthropods developed a complex salivary mixture that can interfere with host haemostatic and immune response, favoring blood acquisition and pathogen transmission. Therefore, a survey of the salivary gland contents can lead to the identification of molecules with potent pharmacological activity in addition to increase our understanding of the molecular mechanisms underlying the hematophagic behaviour of arthropods. The southern house mosquito, Culex quinquefasciatus, is a vector of several pathogenic agents, including viruses and filarial parasites that can affect humans and wild animals. Results Previously, a Sanger-based transcriptome of the salivary glands (sialome) of adult C. quinquefasciatus females was published based on the sequencing of 503 clones organized into 281 clusters. Here, we revisited the southern mosquito sialome using an Illumina-based RNA-sequencing approach of both male and female salivary glands. Our analysis resulted in the identification of 7,539 coding DNA sequences (CDS) that were functionally annotated into 25 classes, in addition to 159 long non-coding RNA (LncRNA). Additionally, comparison of male and female libraries allowed the identification of female-enriched transcripts that are potentially related to blood acquisition and/or pathogen transmission. Conclusion Together, these findings represent an extended reference for the identification and characterization of the proteins containing relevant pharmacological activity in the salivary glands of C. quinquefasciatus mosquitoes.

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“…The recalcification time of human plasma was carried out as described previously ( 33 ). Briefly, 30 μl of normal control plasma (Hyphen BioMed) was mixed with equal volumes of serially diluted Guianensin (3 nM – 126 nM).…”

Section: Methodsmentioning

confidence: 99%

Guianensin, a Simulium guianense salivary protein, has broad anti-hemostatic and anti-inflammatory properties

et al. 2023

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BackgroundSalivary glands from blood-feeding arthropods secrete several molecules that inhibit mammalian hemostasis and facilitate blood feeding and pathogen transmission. The salivary functions from Simulium guianense, the main vector of Onchocerciasis in South America, remain largely understudied. Here, we have characterized a salivary protease inhibitor (Guianensin) from the blackfly Simulium guianense.Materials and methodsA combination of bioinformatic and biophysical analyses, recombinant protein production, in vitro and in vivo experiments were utilized to characterize the molecula mechanism of action of Guianensin. Kinetics of Guianensin interaction with proteases involved in vertebrate inflammation and coagulation were carried out by surface plasmon resonance and isothermal titration calorimetry. Plasma recalcification and coagulometry and tail bleeding assays were performed to understand the role of Guianensin in coagulation.ResultsGuianensin was identified in the sialotranscriptome of adult S. guianense flies and belongs to the Kunitz domain of protease inhibitors. It targets various serine proteases involved in hemostasis and inflammation. Binding to these enzymes is highly specific to the catalytic site and is not detectable for their zymogens, the catalytic site-blocked human coagulation factor Xa (FXa), or thrombin. Accordingly, Guianensin significantly increased both PT (Prothrombin time) and aPTT (Activated partial thromboplastin time) in human plasma and consequently increased blood clotting time ex vivo. Guianensin also inhibited prothrombinase activity on endothelial cells. We show that Guianensin acts as a potent anti-inflammatory molecule on FXa-induced paw edema formation in mice.ConclusionThe information generated by this work highlights the biological functionality of Guianensin as an antithrombotic and anti-inflammatory protein that may play significant roles in blood feeding and pathogen transmission.

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Novel salivary antihemostatic activities of long-form D7 proteins from the malaria vector Anopheles gambiae facilitate hematophagy

Cited by 8 publications

References 42 publications

A deeper insight into the sialome of male and female Ochlerotatus triseriatus mosquitoes

A deeper insight into the sialome of male and female Ochlerotatus triseriatus mosquitoes

A deeper insight into the sialome of male and female Culex quinquefasciatus mosquitoes

Guianensin, a Simulium guianense salivary protein, has broad anti-hemostatic and anti-inflammatory properties

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