scholarly journals Identification of Tick Ixodes ricinus Midgut Genes Differentially Expressed During the Transmission of Borrelia afzelii Spirochetes Using a Transcriptomic Approach

2021 ◽  
Vol 11 ◽  
Author(s):  
Sazzad Mahmood ◽  
Radek Sima ◽  
Veronika Urbanova ◽  
Jos J. A. Trentelman ◽  
Nicolas Krezdorn ◽  
...  

Lyme borreliosis is an emerging tick-borne disease caused by spirochetes Borrelia burgdorferi sensu lato. In Europe, Lyme borreliosis is predominantly caused by Borrelia afzelii and transmitted by Ixodes ricinus. Although Borrelia behavior throughout tick development is quite well documented, specific molecular interactions between Borrelia and the tick have not been satisfactorily examined. Here, we present the first transcriptomic study focused on the expression of tick midgut genes regulated by Borrelia. By using massive analysis of cDNA ends (MACE), we searched for tick transcripts expressed differentially in the midgut of unfed, 24h-fed, and fully fed I. ricinus nymphs infected with B. afzelii. In total, we identified 553 upregulated and 530 downregulated tick genes and demonstrated that B. afzelii interacts intensively with the tick. Technical and biological validations confirmed the accuracy of the transcriptome. The expression of five validated tick genes was silenced by RNA interference. Silencing of the uncharacterized protein (GXP_Contig_30818) delayed the infection progress and decreased infection prevalence in the target mice tissues. Silencing of other genes did not significantly affect tick feeding nor the transmission of B. afzelii, suggesting a possible role of these genes rather in Borrelia acquisition or persistence in ticks. Identification of genes and proteins exploited by Borrelia during transmission and establishment in a tick could help the development of novel preventive strategies for Lyme borreliosis.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Georgia Hurry ◽  
Elodie Maluenda ◽  
Anouk Sarr ◽  
Alessandro Belli ◽  
Phineas T. Hamilton ◽  
...  

AbstractArthropod vectors carry vector-borne pathogens that cause infectious disease in vertebrate hosts, and arthropod-associated microbiota, which consists of non-pathogenic microorganisms. Vector-borne pathogens and the microbiota can both influence the fitness of their arthropod vectors, and hence the epidemiology of vector-borne diseases. The bacterium Borrelia afzelii, which causes Lyme borreliosis in Europe, is transmitted among vertebrate reservoir hosts by Ixodes ricinus ticks, which also harbour a diverse microbiota of non-pathogenic bacteria. The purpose of this controlled study was to test whether B. afzelii and the tick-associated microbiota influence the fitness of I. ricinus. Eggs obtained from field-collected adult female ticks were surface sterilized (with bleach and ethanol), which reduced the abundance of the bacterial microbiota in the hatched I. ricinus larvae by 28-fold compared to larvae that hatched from control eggs washed with water. The dysbiosed and control larvae were subsequently fed on B. afzelii-infected or uninfected control mice, and the engorged larvae were left to moult into nymphs under laboratory conditions. I. ricinus larvae that fed on B. afzelii-infected mice had a significantly faster larva-to-nymph moulting time compared to larvae that fed on uninfected control mice, but the effect was small (2.4% reduction) and unlikely to be biologically significant. We found no evidence that B. afzelii infection or reduction of the larval microbiota influenced the four other life history traits of the immature I. ricinus ticks, which included engorged larval weight, unfed nymphal weight, larva-to-nymph moulting success, and immature tick survival. A retrospective power analysis found that our sampling effort had sufficient power (> 80%) to detect small effects (differences of 5% to 10%) of our treatments. Under the environmental conditions of this study, we conclude that B. afzelii and the egg surface microbiota had no meaningful effects on tick fitness and hence on the R0 of Lyme borreliosis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. J. Klouwens ◽  
J. J. Trentelman ◽  
J. I. Ersoz ◽  
F. Nieves Marques Porto ◽  
R. Sima ◽  
...  

AbstractBB0405 is a surface exposed Borrelia burgdorferi protein and its vaccination protected mice against B. burgdorferi infection. As BB0405 is highly conserved across different B. burgdorferi sensu lato species, we investigated whether vaccination with recombinant BB0405 or through intradermal bb0405 DNA tattoo vaccination could provide protection against different Borrelia species, specifically against Borrelia afzelii, the predominant B. burgdorferi sensu lato genospecies causing Lyme borreliosis across Eurasia. We immunized C3H/HeN mice with recombinant BB0405 or with a codon-optimized bb0405 DNA vaccine using the pVAC plasmid and immunized corresponding control groups mice with only adjuvant or empty vectors. We subsequently subjected these immunized mice to a tick challenge with B. afzelii CB43-infected Ixodes ricinus nymphs. Upon vaccination, recombinant BB0405 induced a high total IgG response, but bb0405 DNA vaccination did not elicit antibody responses. Both vaccine formulations did not provide protection against Borrelia afzelii strain CB43 after tick challenge. In an attempt to understand the lack of protection of the recombinant vaccine, we determined expression of BB0405 and showed that B. afzelii CB43 spirochetes significantly and drastically downregulate the expression of BB0405 protein at 37 °C compared to 33 °C, where as in B. burgdorferi B31 spirochetes expression levels remain unaltered. Vaccination with recombinant BB0405 was previously shown to protect against B. burgdorferi sensu stricto. Here we show that vaccination with either recombinant BB0405 (or non-immunogenic bb0405 DNA), despite being highly conserved among B. burgdorferi sl genospecies, does not provide cross-protection against B. afzelii, mostly likely due to downregulation of this protein in B. afzelii in the mammalian host.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Nienke Hartemink ◽  
Arnold J. H. van Vliet ◽  
Gerrit Gort ◽  
Fedor Gassner ◽  
Frans Jacobs ◽  
...  

Abstract Background The incidence of Lyme borreliosis varies over time and space through as yet incompletely understood mechanisms. In Europe, Lyme borreliosis is caused by infection with a Borrelia burgdorferi (s.l.) genospecies, which is primarily transmitted by a bite of Ixodes ricinus nymphs. The aim of this study was to investigate the spatial and temporal variation in nymphal infection prevalence of B. burgdorferi (s.l.) (NIP), density of questing nymphs (DON) and the resulting density of infected nymphs (DIN). Methods We investigated the infection rates in I. ricinus nymphs that were collected monthly between 2009 and 2016 in 12 locations in the Netherlands. Using generalized linear mixed models, we explored how the NIP, DON and DIN varied during the seasons, between years and between locations. We also determined the genospecies of the Borrelia infections and investigated whether the genospecies composition differed between locations. Results The overall NIP was 14.7%. A seasonal pattern in infection prevalence was observed, with higher estimated prevalences in the summer than in the spring and autumn. This, combined with higher nymphal densities in summer, resulted in a pronounced summer peak in the estimated DIN. Over the 7.5-year study period, a significant decrease in infection prevalence was found, as well as a significant increase in nymphal density. These two effects appear to cancel each other out; the density of infected nymphs, which is the product of NIP × DON, showed no significant trend over years. Mean infection prevalence (NIP, averaged over all years and all months) varied considerably between locations, ranging from 5 to 26%. Borrelia genospecies composition differed between locations: in some locations almost all infections consisted of B. afzelii, whereas other locations had more diverse genospecies compositions. Conclusion In the Netherlands, the summer peak in DIN is a result of peaks in both NIP and DON. No significant trend in DIN was observed over the years of the study, and variations in DIN between locations were mostly a result of the variation in DON. There were considerable differences in acarological risk between areas in terms of infection prevalence and densities of ticks as well as in Borrelia genospecies composition.


2007 ◽  
Vol 297 (2) ◽  
pp. 97-107 ◽  
Author(s):  
Volker Fingerle ◽  
Gereon Goettner ◽  
Lise Gern ◽  
Bettina Wilske ◽  
Ulrike Schulte-Spechtel

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jos J. A. Trentelman ◽  
Julen Tomás-Cortázar ◽  
Sarah Knorr ◽  
Diego Barriales ◽  
Ondrej Hajdusek ◽  
...  

AbstractIn Europe, Ixodes ricinus is the most important vector of human infectious diseases, most notably Lyme borreliosis and tick-borne encephalitis virus. Multiple non-natural hosts of I. ricinus have shown to develop immunity after repeated tick bites. Tick immunity has also been shown to impair B. burgdorferi transmission. Most interestingly, multiple tick bites reduced the likelihood of contracting Lyme borreliosis in humans. A vaccine that mimics tick immunity could therefore potentially prevent Lyme borreliosis in humans. A yeast surface display library (YSD) of nymphal I. ricinus salivary gland genes expressed at 24, 48 and 72 h into tick feeding was constructed and probed with antibodies from humans repeatedly bitten by ticks, identifying twelve immunoreactive tick salivary gland proteins (TSGPs). From these, three proteins were selected for vaccination studies. An exploratory vaccination study in cattle showed an anti-tick effect when all three antigens were combined. However, immunization of rabbits did not provide equivalent levels of protection. Our results show that YSD is a powerful tool to identify immunodominant antigens in humans exposed to tick bites, yet vaccination with the three selected TSGPs did not provide protection in the present form. Future efforts will focus on exploring the biological functions of these proteins, consider alternative systems for recombinant protein generation and vaccination platforms and assess the potential of the other identified immunogenic TSGPs.


2019 ◽  
Vol 286 (1903) ◽  
pp. 20190759 ◽  
Author(s):  
Atle Mysterud ◽  
Dieter J. A. Heylen ◽  
Erik Matthysen ◽  
Aïda Lopez Garcia ◽  
Solveig Jore ◽  
...  

Many vector-borne diseases are transmitted through complex pathogen–vector–host networks, which makes it challenging to identify the role of specific host groups in disease emergence. Lyme borreliosis in humans is now the most common vector-borne zoonosis in the Northern Hemisphere. The disease is caused by multiple genospecies of Borrelia burgdorferi sensu lato bacteria transmitted by ixodid (hard) ticks, and the major host groups transmit Borrelia genospecies with different pathogenicity, causing variable clinical symptoms in humans. The health impact of a given host group is a function of the number of ticks it infects as well as the pathogenicity of the genospecies it carries. Borrelia afzelii , with mainly small mammals as reservoirs, is the most common pathogen causing Lyme borreliosis, and it is often responsible for the largest proportion of infected host-seeking tick nymphs in Europe. The bird-borne Borrelia garinii , though less prevalent in nymphal ticks, is more likely to cause Lyme neuroborreliosis, but whether B. garinii causes disseminated disease more frequently has not been documented. Based on extensive data of annual disease incidence across Norway from 1995 to 2017, we show here that 69% of disseminated Lyme borreliosis cases were neuroborreliosis, which is three times higher than predicted from the infection prevalence of B. garinii in host-seeking ticks (21%). The population estimate of migratory birds, mainly of thrushes, explained part of the annual variation in cases of neuroborreliosis, with a one-year time lag. We highlight the important role of the genospecies' pathogenicity and the host associations for understanding the epidemiology of disseminated Lyme borreliosis.


Author(s):  
Phineas T. Hamilton ◽  
Elodie Maluenda ◽  
Anouk Sarr ◽  
Alessandro Belli ◽  
Georgia Hurry ◽  
...  

The microbiome of blood-sucking arthropods can shape their competence to acquire and maintain infections with vector-borne pathogens. We used a controlled study to investigate the interactions between Borrelia afzelii , which causes Lyme disease in Europe, and the bacterial microbiome of Ixodes ricinus , its primary tick vector. We applied a surface sterilization treatment to I. ricinus eggs to produce dysbiosed tick larvae that had a much lower bacterial abundance and a changed bacterial microbiome compared to the control larvae. Dysbiosed and control larvae were fed on B. afzelii -infected mice and uninfected control mice and the engorged larvae were left to molt into nymphs, which were tested for B. afzelii infection and their bacterial microbiome by 16S rRNA amplicon sequencing. Surprisingly, larval dysbiosis had no effect on the vector competence of I. ricinus for B. afzelii , as the nymphal infection prevalence and the nymphal spirochete load were the same between the dysbiosed group and the control group. The strong effect of egg surface sterilization on the tick bacterial microbiome largely disappeared once the larvae molted into nymphs. The most important determinant of the bacterial microbiome of I. ricinus nymphs was the B. afzelii infection status of the mouse on which the nymphs had fed as larvae. Nymphs that had taken their larval blood meal from an infected mouse had a less abundant but more diverse bacterial microbiome compared to control nymphs. Our study demonstrates that vector-borne infections in the vertebrate host shape the microbiome of the arthropod vector. IMPORTANCE Many blood-sucking arthropods transmit pathogens that cause infectious disease. For example, Ixodes ricinus ticks transmit the bacterium Borrelia afzelii , which causes Lyme disease in humans. Ticks also have a microbiome, which can influence their ability to acquire and transmit tick-borne pathogens like B. afzelii . We sterilized I. ricinus eggs with bleach, and the tick larvae that hatched from these eggs had a dramatically reduced and changed bacterial microbiome compared to control larvae. These larvae were fed on B. afzelii -infected mice and the resultant nymphs were tested for B. afzelii and their bacterial microbiome. We found that our manipulation of the bacterial microbiome had no effect on the ability of the tick larvae to acquire and maintain populations of B. afzelii . In contrast, we found that B. afzelii infection had dramatic effects on the bacterial microbiome of I. ricinus nymphs. Our study demonstrates that infections in the vertebrate host can shape the tick microbiome.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Georgia Hurry ◽  
Elodie Maluenda ◽  
Anouk Sarr ◽  
Alessandro Belli ◽  
Phineas T. Hamilton ◽  
...  

1951 ◽  
Vol 41 (3) ◽  
pp. 469-485 ◽  
Author(s):  
G. Owen Evans

Ixodes ricinus is the common tick infesting farmstock in Wales. Dermacentor reticulatus is recorded on cattle and sheep on two farms in N. Cardiganshire.I. ricinus is widely distributed in the four major grassland zones of N.W. Cardiganshire. The most extensive areas of tick infestation are found on the marginal and hill farms. In lowland areas, except on extensive stretches of marshland, infested pastures are confined to isolated tracts of badly managed or poorly drained land. Infested grazings are invariably “rough” and contain one of the following plants as dominant: Festuca spp., Agrostis spp., Molinia caerulea, Nardus stricta, Pteris aquilina or Juncus spp. The degree of infestation of cattle depends on the relative area of the available grazing land colonised by the tick. Continuous stocking of infested pastures results in heavy infestations and vice versa.Bovine piroplasmosis is the major tick-borne disease in N.W. Cardiganshire and predominates in the lowland districts. Outbreaks of the disease on marginal and hill farms are generally infrequent. Reasons are suggested for this phenomenon. Tick pyaemia is confined to lambs on hill grazings. The incidence of this disease is low.The distribution of the tick in Wales and the border counties of Hereford and Salop shows a general relationship to areas of rough grazing. The tick is widespread in the western counties and is almost absent in the border counties. Radnorshire and Breconshire are interesting in that they have few infested farms in relation to the extensive nature of the “rough” grazing. A survey has also been conducted of the incidence of bovine piroplasmosis in Wales.


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