Dataset Information

Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata.

ABSTRACT: The saliva of blood-feeding parasites is a rich source of peptidase inhibitors that help to overcome the host's defence during host-parasite interactions. Using proteomic analysis, the cystatin OmC2 was demonstrated in the saliva of the soft tick Ornithodoros moubata, an important disease vector transmitting African swine fever virus and the spirochaete Borrelia duttoni. A structural, biochemical and biological characterization of this peptidase inhibitor was undertaken in the present study. Recombinant OmC2 was screened against a panel of physiologically relevant peptidases and was found to be an effective broad-specificity inhibitor of cysteine cathepsins, including endopeptidases (cathepsins L and S) and exopeptidases (cathepsins B, C and H). The crystal structure of OmC2 was determined at a resolution of 2.45 A (1 A=0.1 nm) and was used to describe the structure-inhibitory activity relationship. The biological impact of OmC2 was demonstrated both in vitro and in vivo. OmC2 affected the function of antigen-presenting mouse dendritic cells by reducing the production of the pro-inflammatory cytokines tumour necrosis factor alpha and interleukin-12, and proliferation of antigen-specific CD4+ T-cells. This suggests that OmC2 may suppress the host's adaptive immune response. Immunization of mice with OmC2 significantly suppressed the survival of O. moubata in infestation experiments. We conclude that OmC2 is a promising target for the development of a novel anti-tick vaccine to control O. moubata populations and combat the spread of associated diseases.

SUBMITTER: Salat J

PROVIDER: S-EPMC3523712 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata.

Salát Jirí J Paesen Guido C GC Rezácová Pavlína P Kotsyfakis Michalis M Kovárová Zuzana Z Sanda Miloslav M Majtán Juraj J Grunclová Lenka L Horká Helena H Andersen John F JF Brynda Jirí J Horn Martin M Nunn Miles A MA Kopácek Petr P Kopecký Jan J Mares Michael M

The Biochemical journal 20100701 1

The saliva of blood-feeding parasites is a rich source of peptidase inhibitors that help to overcome the host's defence during host-parasite interactions. Using proteomic analysis, the cystatin OmC2 was demonstrated in the saliva of the soft tick Ornithodoros moubata, an important disease vector transmitting African swine fever virus and the spirochaete Borrelia duttoni. A structural, biochemical and biological characterization of this peptidase inhibitor was undertaken in the present study. Rec ...[more]

PMID: 20545626

Similar Datasets

Project description:IntroductionOrnithodoros erraticus and Ornithodoros moubata are the main vectors of African swine fever virus (ASFV) and the human relapsing fever spirochetes Borrelia hispanica and Borrelia crocidurae in the Mediterranean region and Borrelia duttoni in continental Africa. Manipulation of the tick microbiome has been shown to reduce vector fitness and competence in tick vectors, suggesting that the identification of key microbial players associated with tick tissues can inform interventions such as anti-microbiota vaccines to block pathogen development in the midgut and/or salivary glands.MethodsIn this study, we analyzed and compared the microbiome of the salivary glands and midgut of O. erraticus and O. moubata. For the taxonomic and functional characterization of the tissue-specific microbiome, we used 16S rRNA amplicon sequencing and prediction of metabolic profiles using PICRUSt2. Co-occurrence networks were built to characterize the community assembly and identify keystone taxa in each tick species.ResultsOur results revealed differences in the composition, diversity, and assembly of the bacterial microbiome of salivary glands and midgut within each tick species, but differences were more noticeable in O. moubata. Differences were also found in the microbiome of each tissue, salivary gland and midgut, between species. However, the 'Core Association Networks (CAN)' analysis revealed conserved patterns of interacting taxa in tissues within and between tick species. Different keystone taxa were identified in O. erraticus and O. moubata tissues, but Muribaculaceae and Alistipes were found as keystone taxa in the salivary glands of both tick species which justifies their use as anti-microbiota vaccine candidates to alter the microbiome and reduce tick fitness and/or block pathogen transmission. The high similarity of predicted metabolic pathways profiles between tissues of the two tick species suggests that taxonomic variability of the microbiome is not associated with significant changes in microbial functional profiles.ConclusionWe conclude that the taxonomic structure of the microbiome in O. erraticus and O. moubata is tissue-specific, suggesting niche partitioning of bacterial communities associated to these soft ticks. However, shared keystone taxa and conserved patterns of interacting taxa between tissues and tick species suggest the presence of key microbial players that could be used as anti-microbiota vaccine candidates to affect tick physiology and/or pathogen colonization.

Project description:African swine fever (ASF) is a lethal hemorrhagic disease in domestic pigs and wild suids caused by African swine fever virus (ASFV), which threatens the swine industry globally. In its native African enzootic foci, ASFV is naturally circulating between soft ticks of the genus Ornithodoros, especially in the O. moubata group, and wild reservoir suids, such as warthogs (Phacochoerus spp.) that are bitten by infected soft ticks inhabiting their burrows. While the ability of some Afrotropical soft ticks to transmit and maintain ASFV is well established, the vector status of Palearctic soft tick species for ASFV strains currently circulating in Eurasia remains largely unknown. For example, the Iberian soft tick O. erraticus is a known vector and reservoir of ASFV, but its ability to transmit different ASFV strains has not been assessed since ASF re-emerged in Europe in 2007. Little is known about vector competence for ASFV in other species, such as O. verrucosus, which occurs in southern parts of Eastern Europe, including Ukraine and parts of Russia, and in the Caucasus. Therefore, we conducted transmission trials with two Palearctic soft tick species, O. erraticus and O. verrucosus, and the Afrotropical species O. moubata. We tested the ability of ticks to transmit virulent ASFV strains, including one of direct African origin (Liv13/33), and three from Eurasia that had been involved in previous (OurT88/1), and the current epizooties (Georgia2007/1 and Ukr12/Zapo). Our experimental results showed that O. moubata was able to transmit the African and Eurasian ASFV strains, whereas O. erraticus and O. verrucosus failed to transmit the Eurasian ASFV strains. However, naïve pigs showed clinical signs of ASF when inoculated with homogenates of crushed O. erraticus and O. verrucosus ticks that fed on viraemic pigs, which proved the infectiousness of ASFV contained in the ticks. These results documented that O. erraticus and O. verrucosus are unlikely to be capable vectors of ASFV strains currently circulating in Eurasia. Additionally, the persistence of infection in soft ticks for several months reaffirms that the infectious status of a given tick species is only part of the data required to assess its vector competence for ASFV.

Dataset Information

Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata.

Publications

Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets