Cloning of a salivary gland metalloprotease and characterization of gelatinase and fibrin(ogen)lytic activities in the saliva of the Lyme disease tick vector Ixodes scapularis

Abstract Background Metagenomic studies have revealed the presence of a filarial nematode in Ixodes scapularis. The phylogeny of this agent, and its potential for human infection, are unknown.Methods We used existing metagenomic data from I. scapularis to determine the phylogeny of this tick-associated nematode and employed quantitative PCR to determine if the presence of this agent had an effect on the burden of Borrelia burgdorferi. We also developed a Luciferase Immunoprecipitation System assay using the Av33 antigen as a target to investigate the presence of antibodies against this nematode in 128 serum specimens from patients with Lyme disease and babesiosis. To demonstrate assay utility, we used 15 sera from patients with onchocerciasis as controls.Results We show that this agent is a new species in the genus Monanema and its presence in vector ticks does not impact the burden of B. burgdorferi. We did not detect IgG antibodies to this agent in 127 of 128 sera from patients with Lyme disease or babesiosis. One sample had reactivity above the threshold, but at the low-level equivalent to the least reactive onchocerciasis sera. This low positive signal could be a result of cross-reacting antibodies, antibodies from a previous infection with a filarial nematode, or, less likely, a exposure to the Ixodes scapularis-associated nematode. Conclusions We found no evidence that this nematode contributes to the spectrum of human tick-borne infections.

Download Full-text

Penthalaris, a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis

Thrombosis and Haemostasis ◽

10.1160/th03-11-0715 ◽

2004 ◽

Vol 91 (05) ◽

pp. 886-898 ◽

Cited By ~ 77

Author(s):

Thomas Mather ◽

José Ribeiro ◽

Ivo Francischetti

Keyword(s):

Salivary Gland ◽

Lyme Disease ◽

Tissue Factor ◽

Tissue Factor Pathway Inhibitor ◽

Factor Viia ◽

Ixodes Scapularis ◽

Gel Filtration ◽

Factor X ◽

Tick Saliva ◽

Tissue Factor Pathway

SummaryTick saliva is a rich source of molecules with antiinflammatory, antihemostatic and immunosupressive properties. In this paper, a novel tick salivary gland cDNA with sequence homology to tissue factor pathway inhibitor (TFPI) and coding for a protein called Penthalaris has been characterized from the Lyme disease vector, Ixodes scapularis. Penthalaris is structurally unique and distinct from TFPI or TFPI-like molecules described so far, including Ixolaris, NAPc2, TFPI-1 and TFPI-2. Penthalaris is a 308-amino-acid protein (35 kDa, pI 8.58) with 12 cysteine bridges and 5 tandem Kunitz domains. Recombinant Penthalaris was expressed in insect cells and shown to inhibit factor VIIa (FVIIa)/tissue factor(TF)-induced factor X (FX) activation with an IC50 of ∼ 100 pM. Penthalaris tightly binds both zymogen FX and enzyme FXa (exosite), but not FVIIa, as demonstrated by column gel-filtration chromatography. At high concentrations, Penthalaris attenuates FVIIa/TF-induced chromogenic substrate (S2288) hydrolysis and FIX activation. In the presence of DEGR-FX or DEGR-FXa, but not des-Gla-DEGR-FXa as scaffolds, tight and stoichiometric inhibition of FVIIa/TF was achieved. In addition, Penthalaris blocks cell surface-mediated FXa generation by monomer (de-encrypted), but not dimer (encrypted) TF in HL-60 cells. Penthalaris may act in concert with Ixolaris and other salivary anti-hemostatics in order to help ticks to successfully feed on blood. Penthalaris is a novel anticoagulant and a tool to study FVIIa/TF-initiated biologic processes.

Download Full-text

Recent and rapid population growth and range expansion of the Lyme disease tick vector,Ixodes scapularis, in North America

Evolution ◽

10.1111/evo.12690 ◽

2015 ◽

Vol 69 (7) ◽

pp. 1678-1689 ◽

Cited By ~ 25

Author(s):

Camilo E. Khatchikian ◽

Melissa A. Prusinski ◽

Melissa Stone ◽

Peter Bryon Backenson ◽

Ing-Nang Wang ◽

...

Keyword(s):

North America ◽

Lyme Disease ◽

Population Growth ◽

Range Expansion ◽

Ixodes Scapularis ◽

Rapid Population Growth ◽

Tick Vector

Download Full-text

Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete

Cell Host & Microbe ◽

10.1016/j.chom.2013.12.001 ◽

2014 ◽

Vol 15 (1) ◽

pp. 58-71 ◽

Cited By ~ 144

Author(s):

Sukanya Narasimhan ◽

Nallakkandi Rajeevan ◽

Lei Liu ◽

Yang O. Zhao ◽

Julia Heisig ◽

...

Keyword(s):

Lyme Disease ◽

Gut Microbiota ◽

Ixodes Scapularis ◽

Tick Vector

Download Full-text

Implications of climate change on the distribution of the tick vector Ixodes scapularis and risk for Lyme disease in the Texas-Mexico transboundary region

Parasites & Vectors ◽

10.1186/1756-3305-7-199 ◽

2014 ◽

Vol 7 (1) ◽

pp. 199 ◽

Cited By ~ 47

Author(s):

Teresa P Feria-Arroyo ◽

Ivan Castro-Arellano ◽

Guadalupe Gordillo-Perez ◽

Ana L Cavazos ◽

Margarita Vargas-Sandoval ◽

...

Keyword(s):

Climate Change ◽

Lyme Disease ◽

Ixodes Scapularis ◽

Tick Vector

Download Full-text

Identification and functional characterization of a pyrokinin neuropeptide receptor in the Lyme disease vector, Ixodes scapularis

Peptides ◽

10.1016/j.peptides.2016.09.011 ◽

2016 ◽

Vol 86 ◽

pp. 42-54 ◽

Cited By ~ 13

Author(s):

Kinsi Gondalia ◽

Anam Qudrat ◽

Brigida Bruno ◽

Janet Fleites Medina ◽

Jean-Paul V. Paluzzi

Keyword(s):

Lyme Disease ◽

Ixodes Scapularis ◽

Functional Characterization ◽

Disease Vector

Download Full-text

The effect of infection with Lyme disease spirochetes (Borrelia burgdorferi) on the phototaxis, activity, and questing height of the tick vector Ixodes scapularis

Parasitology ◽

10.1017/s0031182000066336 ◽

1996 ◽

Vol 113 (2) ◽

pp. 97-103 ◽

Cited By ~ 33

Author(s):

H. Lefcort ◽

L. A. Durden

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Kin Selection ◽

Ixodes Scapularis ◽

Bacterial Pathogen ◽

Pathogen Transmission ◽

Ecological Effects ◽

Infected Tick ◽

Tick Vector ◽

Tick Vectors

SUMMARYLittle is known about the effects of infection with Borrelia burgdorferi, the bacterium that causes Lyme disease, on its tick vectors. The purpose of this study was to determine the behavioural and ecological effects of infection by the bacterium in nymphal and adult black-legged (Ixodes scapularis) ticks. We found that the effects of infection were more pronounced in adults than in nymphs. Compared to uninfected adults, infected adults were less able to overcome physical obstacles, avoided vertical surfaces, were less active and quested at lower heights. Infected nymphs showed increased phototaxis and attraction to vertical surfaces. Infected nymphs also showed trends toward increased questing height and a greater tendency to overcome physical obstacles although these trends were not statistically significant. These altered behaviours in an infected tick may affect survival or pathogen transmission and may reflect kin selection in the bacterial pathogen.

Download Full-text

Genomic insights into the Ixodes scapularis tick vector of Lyme disease

Nature Communications ◽

10.1038/ncomms10507 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 238

Author(s):

Monika Gulia-Nuss ◽

Andrew B. Nuss ◽

Jason M. Meyer ◽

Daniel E. Sonenshine ◽

R. Michael Roe ◽

...

Keyword(s):

Lyme Disease ◽

Ixodes Scapularis ◽

Tick Vector

Download Full-text

Characterization of a Monanema nematode in Ixodes scapularis

10.21203/rs.3.rs-24916/v1 ◽

2020 ◽

Author(s):

Rafal Tokarz ◽

Teresa Tagliafierro ◽

W. Ian Lipkin ◽

Adriana R Marques

Keyword(s):

Lyme Disease ◽

Ixodes Scapularis ◽

Human Infection ◽

Filarial Nematode ◽

Metagenomic Data ◽

Igg Antibodies ◽

Positive Signal ◽

Previous Infection ◽

A New Species

Abstract Background Metagenomic studies have revealed the presence of a filarial nematode in Ixodes scapularis. The phylogeny of this agent, and its potential for human infection, are unknown.Methods We used existing metagenomic data from I. scapularis to determine the phylogeny of this tick-associated nematode and employed quantitative PCR to determine if the presence of this agent had an effect on the burden of Borrelia burgdorferi. We also developed a Luciferase Immunoprecipitation System assay using the Av33 antigen as a target to investigate the presence of antibodies against this nematode in 128 serum specimens from patients with Lyme disease and babesiosis. To demonstrate assay utility, we used 15 sera from patients with onchocerciasis as controls.Results We show that this agent is a new species in the genus Monanema and its presence in vector ticks does not impact the burden of B. burgdorferi. We did not detect IgG antibodies to this agent in 127 of 128 sera from patients with Lyme disease or babesiosis. One sample had reactivity above the threshold, but at the low-level equivalent to the least reactive onchocerciasis sera. This low positive signal could be a result of cross-reacting antibodies, antibodies from a previous infection with a filarial nematode, or, less likely, a exposure to the Ixodes scapularis-associated nematode.Conclusions We found no evidence that this nematode contributes to the spectrum of human tick-borne infections.

Download Full-text