Anticoagulant activity in salivary gland homogenates of Thyrsopelma guianense (Diptera: Simuliidae), the primary vector of onchocerciasis in the Brazilian Amazon

Chagas, Andrezza Campos; Medeiros, Jansen Fernandes; Astolfi-Filho, Spártaco; Py-Daniel, Victor

doi:10.1590/s0074-02762010000200011

Cited by 6 publications

(6 citation statements)

References 37 publications

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“…Consequently, Guianensin inhibited the amidolytic activity of FXa; however, no thrombin inhibition was observed ( Figure 2D ). These findings are consistent with the anticoagulant activity reported in salivary gland extracts of S. guianense ( 9 ).…”

Section: Resultssupporting

confidence: 92%

“…Accordingly, Guianensin also blocked prothrombinase activity in vitro ( Supplementary Figure S3 ). Taken together, our results indicate that Guianensin is a salivary FXa-directed anticoagulant in S. guianense and may account for the anti-FXa activity found in salivary gland extracts previously described for this species ( 9 ).…”

Section: Resultssupporting

confidence: 82%

“…Most research has focused on the only species of black fly that has been successfully colonized in the laboratory, Simulium vittatum ( 8 ). However, Simulium guianense is the primary vector of O. volvulus in the Latin American endemic region on the border of Brazil and Venezuela ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

“…Structural similarities between common serine proteases allow a single Kunitz inhibitor to have activity against a broad range of enzymes, thus providing a multifunctional role in inhibiting a variety of host processes ( 25 , 28 ). The anticoagulant activity of S. guianense salivary gland homogenate has been characterized, but the specific molecules involved have not yet been identified ( 9 ). The sialome of S. guianense described proteins in the salivary glands with potential importance for blood feeding and disease transmission, and a secreted Kunitz-type protein was identified that we, henceforth, call Guianensin ( 29 ).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…Kunitz-domain proteins were seen in all black fly sialotranscriptomes. Probably this family is responsible for the anticoagulant activity previously related to SGHs in S. guianense [137]. …”

Section: Discussionmentioning

confidence: 99%

An insight into the sialome of Simulium guianense (DIPTERA:SIMulIIDAE), the main vector of River Blindness Disease in Brazil

et al. 2011

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BackgroundLittle is known about the composition and function of the saliva in black flies such as Simulium guianense, the main vector of river blindness disease in Brazil. The complex salivary potion of hematophagous arthropods counteracts their host's hemostasis, inflammation, and immunity.ResultsTranscriptome analysis revealed ubiquitous salivary protein families--such as the Antigen-5, Yellow, Kunitz domain, and serine proteases--in the S. guianense sialotranscriptome. Insect-specific families were also found. About 63.4% of all secreted products revealed protein families found only in Simulium. Additionally, we found a novel peptide similar to kunitoxin with a structure distantly related to serine protease inhibitors. This study revealed a relative increase of transcripts of the SVEP protein family when compared with Simulium vittatum and S. nigrimanum sialotranscriptomes. We were able to extract coding sequences from 164 proteins associated with blood and sugar feeding, the majority of which were confirmed by proteome analysis.ConclusionsOur results contribute to understanding the role of Simulium saliva in transmission of Onchocerca volvulus and evolution of salivary proteins in black flies. It also consists of a platform for mining novel anti-hemostatic compounds, vaccine candidates against filariasis, and immuno-epidemiologic markers of vector exposure.

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Glandular Matrices and Secretions: Blood-Feeding Arthropods

Mans

2016

Extracellular Composite Matrices in Arthropods

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Anticoagulant activity in salivary gland homogenates of Thyrsopelma guianense (Diptera: Simuliidae), the primary vector of onchocerciasis in the Brazilian Amazon

Abstract: In this study, anticoagulant activity was detected in salivary gland homogenates (SGHs)

Cited by 6 publications

References 37 publications

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

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

An insight into the sialome of Simulium guianense (DIPTERA:SIMulIIDAE), the main vector of River Blindness Disease in Brazil

Glandular Matrices and Secretions: Blood-Feeding Arthropods

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