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| Key features of pathogen transmission by Ixodes scapularis. The tick life stages involved in the transmission of a typical pathogen (outer ring) and critical physical/physiological barriers to pathogen acquisition, replication and transmission (inner circle) are depicted. Representative pathogens: (a) Borrelia spp.; (b) Anaplasma phagocytophilum; (c) Tick-borne flavivirus (e.g., Langat virus, LGTV). The different strategies employed by a parasite to navigate from the midgut to the salivary glands, and tick and parasite derived factors known to facilitate these processes are shown. IMD, Immunodeficiency; JAK-STAT, Janus Kinase/Signal Transsducers and Activators of Transcription; OspA, Borrelia outer surface protein A; Salp15/16, salivary gland protein 15/16; tHRF, tick histamine-release factor; TROPSA, tick receptor for OspA; TSLP1, tick salivary lectin pathway inhibitor.
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Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-tr...
Contexts in source publication
Context 1
... as vectors of pathogens and parasites. Ticks are biological vectors of viruses, bacteria and protozoa that are typically acquired via the blood meal and transmitted through saliva during feeding (Fig. 5). The tick immune system has several mechanisms to fend off pathogen invasion. Most components of the Toll, IMD (Immunodeficiency), JAK-STAT (Janus Kinase/ Signal Transducers and Activators of Transcription) immune pathways and the RNA interference-antiviral signalling pathways were identified in the tick genome (Supplementary Figs 22 ...
Context 2
... infection factors facilitate transmission of the Lyme disease pathogen, Borrelia burgdorferi (Fig. 5). These include the tick salivary gland proteins Salp15, Salp20, Salp25D, tick salivary lectin pathway inhibitor and tick histamine-release factor, as well as the tick receptor for OspA and tick protein tre31, and the Borrelia lipoprotein BBE31 (ref. 51). Increasingly, research is focused on interactions with Anaplasma phagocytophilum ...
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Citations
... Low quality reads after mapping to reference genomes (MAPQ < 20) were excluded from downstream analysis. Due to the high number of repeats in the tick genome(Cramaro et al., 2015;De et al., 2023;Gulia-Nuss et al., 2016;Jia et al., 2020), all reads which had coverage above 100× were removed. F I G U R E 2 Geographical distribution of Finnish samples. ...
Identifying hybridization between common pathogen vectors is essential due to the major public health implications through risks associated with hybrid's enhanced pathogen transmission potential. The hard‐ticks Ixodes ricinus and Ixodes persulcatus are the two most common vectors of tick‐borne pathogens that affect human and animal health in Europe. Ixodes ricinus is a known native species in Finland with a well‐known distribution, whereas I. persulcatus has expanded in range and abundance over the past 60 years, and currently it appears the most common tick species in certain areas in Finland. Here we used double‐digest restriction site‐associated DNA (ddRAD) sequencing on 186 ticks (morphologically identified as 92 I. ricinus, and 94 I. persulcatus) collected across Finland to investigate whether RAD generated single nucleotide polymorphisms (SNPs) can discriminate tick species and identify potential hybridization events. Two different clustering methods were used to assign specific species based on how they clustered and identified hybrids among them. We were able to discriminate between the two tick species and identified 11 putative hybrids with admixed genomic proportions ranging from approximately 24 to 76 percent. Four of these hybrids were morphologically identified as I. ricinus while the remaining seven were identified as I. persulcatus. Our results thus indicate that RAD SNPs are robust in identifying both species of the ticks as well as putative hybrids. These results further suggest ongoing hybridization between I. ricinus and I. persulcatus in their natural populations in Finland. The unique ability of RAD markers to discriminate between tick species and hybrids adds a useful aspect to tick evolutionary studies. Our findings align with previous studies and suggest a shared evolutionary history between the species, with instances of individuals possessing a considerable proportion of the other species' genome. This study is a significant step in understanding the formation of hybridization zones due to range expansion potentially associated with climate change.
... The black-legged tick, Ixodes scapularis, is the vector of several human pathogens, including those causing Lyme disease 7 . The life cycle of I. scapularis is approximately two to four years 8 . During this time, ticks cycle through four stages: egg, larva, nymph, and adult. ...
Numerous feeding studies on tick species have explored disease transmission, vector interactions, and acaricide testing. Traditionally, these studies used animals for feeding. However, artificial membrane feeding offers several advantages including increased standardization of experiments, decreased costs, and improved animal welfare. In vitro conditions must closely mimic natural environments to promote successful feeding attachment. Kairomones produced by the host are strong stimulants that encourage attachment. An important kairomone detected by ticks is carbon dioxide (CO2). Previous studies have shown elevated CO2 levels stimulate host identification and attraction and potentially improve artificial feeding rates in some tick species. The objective of this study was to use an artificial membrane feeding chamber prototype to explore the effects of ambient CO2 in inducing Ixodes scapularis attachment. Differences in attachment rate were explored at an air-typical ambient CO2 level of 0.04% and an elevated CO2 level of 4.0%. Tick attachment was not detected in either ambient CO2 condition during the incubation period, indicating ambient CO2 does not impact the attachment rate under the presented condition. However, I. scapularis contact with the artificial membrane occurred at an increased rate of 0.014 female ticks in contact with the membrane per hour in the elevated CO2 condition (4%) compared with a rate of 0.01 ticks per hour in the air-typical CO2 condition (0.04%) (p = 0.048) suggesting that the ambient CO2 level affects attraction to the blood but does not directly stimulate attachment of I. scapularis.
... Alternatively, hemimetabolous insects and other arthropods that characteristically do not liberate their gut bacteria during metamorphosis, may possess an ancestral incomplete (relative to holometabolous vectors and Drosophila) Imd pathway. For example, the tick Ixodes scapularis lacks genes encoding upstream regulators of the Imd pathway, including Imd, and FADD [313]. Despite the absence of these regulators, the remaining Imd pathway is active against infection by tick-borne pathogenic bacteria such as Borrelia burgdorferi and is triggered by cellular stress responses centring on the evolutionary conserved Unfolded Protein Response (UPR) [314]. ...
This overview initially describes insect immune reactions and then brings together present knowledge of the interactions of vector insects with their invading parasites and pathogens. It is a way of introducing this special issue with subsequent papers presenting the latest details of these interactions in each particular group of vectors. Hopefully, this paper will fill a void in the literature since brief descriptions of vector immunity have now been brought together in one publication and could form a starting point for those interested and new to this important area. Descriptions are given on the immune reactions of mosquitoes, blackflies, sandflies, tsetse flies, lice, fleas and triatomine bugs. Cellular and humoral defences are described separately but emphasis is made on the co-operation of these processes in the completed immune response. The paper also emphasises the need of great care in extracting haemocytes for subsequent study as appreciation of their fragile nature is sometimes overlooked with non-sterile media, smearing techniques and excessive centrifugation sometimes used. The potential vital role of eicosanoids in the instigation of many of the immune reactions described is also discussed. Finally, the priming of the immune system, mainly in mosquitoes, is considered and one possible mechanism is presented
... (f) Discovery and characterization of tick Subolesin, a conserved protein involved in the regulation of innate immune response and other biological processes, with protective capacity as a tick vaccine [15,16]. (g) Characterization of host-vector-pathogen molecular interactions to understand the mechanisms involved in pathogen infection, multiplication and transmission, and vaccine development [17][18][19][20][21][22][23]. (h) Characterization of biomolecules/biomarkers such as alpha-Gal in infectious and allergic diseases [24][25][26][27][28]. ...
Autobiographical scientometrics studies of established scientists are rare but may contribute to
guidance for young researchers. This study covered my 40-years career in Life Sciences and Biomedicine by
focusing on bibliometric analysis of scientific publications and other papers and patents. Data included 811
papers published in international journals and book chapters and 6 books edited. Total citations for these
publications are 44923 with author’s 98 H-index and 521 i10-index according to the Google scholar profile.
Correlation was not found between citations and the number of publications per research area, journal H-
index or journal impact factor (IF). Data included 36 patents in the areas of pharmaceutical, transgenesis,
vaccine, formulation, probiotic and diagnostic. Three of these patents resulted in products registered and
commercialized. Students are highlighted as key components of research with 36 Ph.D. thesis supervised and
6 thesis under supervision. Lessons from this study contributing to guidance for young scientists include that
quality of research is the priority together with productivity but considering what, when and where to publish
not only based on journal IF, H-index and quartile (Q).Inter- and multi-disciplinary international
collaborations in research and co-authorship in review and method papers contribute to research quality and
to advance in scientific career. Projects leading to patent applications and products improve scientific and
social impact of research. Additionally, communication of results in social media is important to promote
research and scientific career, and exploration of other areas such as humanities, art and music contributes to
inspiration and imaginative research approaches.
... In addition, these signaling molecules are well known for acting as neuromodulators in the circuits of the central nervous system [31]. As of today, in the tick central nervous system, the synganglion, 38 different neuropeptide genes have been identified [32,33]. Among those, multiple have been immunolocalized in distinct neuronal cells within the synganglion as well as in their axons reaching several visceral organs [34][35][36][37]. ...
Anthropogenic electromagnetic radiation is an important environmental factor affecting the functionality of biological systems. Sensitivity to various frequencies of electromagnetic radiation has been detected in ixodid ticks in the past. However, the physiological aspects of radiation effects have not yet been studied in ticks. In the presented experiment, 360 Ixodes ricinus ticks, 180 males and 180 females, were divided into 16 irradiated and 8 control groups. The irradiated groups were exposed to two different intensities of electromagnetic radiation with a frequency of 900 MHz at different lengths of exposure time. RT-PCR was utilized to determine the changes in mRNA levels in tick synganglia after irradiation. Four randomly selected neuropeptide genes were tested-allatotropin (at), FGLa-related allatostatins (fgla/ast), kinin, and arginine-vasopressin-like peptide (avpl). A significant decrease in transcript levels in all female groups exposed to higher intensity radiofrequency radiation for 1 to 3 h was found. After one hour of radiofrequency exposure, a significant downregulation in allatotropin expression in males was detected. A consistent downreg-ulation of the at gene was detected in males irradiated with at a higher intensity. Unfortunately, the specific functions of the studied neuropeptides in ticks are not known yet, so a more comprehensive study is necessary to describe the effects of EMF on observed neuropeptides. This study represents the first report on the effects of the abiotic environment on tick neurophysiology.
... Genetic studies including nuclear genes or single nucleotide polymorphisms (SNPs) have been proposed as suitable for resolving specific identities of ticks [11,12]. Individual gene markers, microsatellites, or SNPs have been used for some species of ticks to explore hybridization, mitochondrial introgression, phylogenetic relationships, interspecific variation, and comparison between mitochondrial and nuclear markers for species/lineage delimitation [13][14][15][16][17]. ...
This study addresses the variability of the mitochondrial cytochrome oxidase subunit I (COI) and 16S rDNA (16S), and nuclear internal transcriber spacer ITS2 (ITS2) genes in a set of field-collected samples of the cattle tick, Rhipicephalus microplus (Canestrini, 1888), and in geo-referenced sequences obtained from GenBank. Since the tick is currently considered to be a complex of cryptic taxa in several regions of the world, the main aims of the study are (i) to provide evidence of the clades of the tick present in the Neotropics, (ii) to explore if there is an effect of climate traits on the divergence rates of the target genes, and (iii) to check for a relationship between geographical and genetic distance among populations (the closest, the most similar, meaning for slow spread). We included published sequences of Rhipicephalus annulatus (Nearctic, Afrotropical, and Mediterranean) and R. microplus (Afrotropical, Indomalayan) to fully characterize the Neotropical populations (total: 74 16S, 44 COI, and 49 ITS2 sequences included in the analysis). Only the clade A of R. microplus spread in the Nearctic–Neotropics. Both the K and Lambda’s statistics, two measures of phylogenetic signal, support low divergence rates of the tested genes in populations of R. microplus in the Neotropics. These tests demonstrate that genetic diversity of the continental populations does not correlate either with the geographic distance among samples or with environmental variables. The low variability of these genes may be due to a combination of factors like (i) the recent introduction of the tick in the Neotropics, (ii) a large, effective, and fast exchange of populations, and (iii) a low effect of climate on the evolution rates of the target genes. These results have implications for the ecological studies and control of cattle tick infestations.
... The first attempt at sequencing a tick genome was initiated in 2008 using embryos from the Wikel strain of I. scapularis Wikel (IscaW1). The IscaW1 genome was eventually published in 2016 (Gulia-Nuss et al, 2016). This assembly was highly fragmented (total number of scaffolds = 369,495) and suffered from short contigs (contig N50, 2,942 bp, meaning that only half of the assembly was found on contigs >3 kb) and a total length of combined scaffolds (including gaps) of 1.8 Gbp. ...
Ixodes scapularis , the black-legged tick, is the principal vector of the Lyme disease spirochete, Borrelia burgdorferi , and is responsible for most of the ∼470,000 estimated Lyme disease cases annually in the USA. Ixodes scapularis can transmit six additional pathogens of human health significance. Because of its medical importance, I. scapularis was the first tick genome to be sequenced and annotated. However, the first assembly, I. scapularis Wikel (IscaW), was highly fragmented because of the technical challenges posed by the long, repetitive genome sequences characteristic of arthropod genomes and the lack of long-read sequencing techniques. Although I. scapularis has emerged as a model for tick research because of the availability of new tools such as embryo injection and CRISPR-Cas9-mediated gene editing yet the lack of chromosome-scale scaffolds has slowed progress in tick biology and the development of tools for their control. Here we combine diverse technologies to produce the I. scapularis Gulia-Nuss (IscGN) genome assembly and gene set. We used DNA from eggs and male and female adult ticks and took advantage of Hi-C, PacBio HiFi sequencing, and Illumina short-read sequencing technologies to produce a chromosome-level assembly. In this work, we present the predicted pseudochromosomes consisting of 13 autosomes and the sex pseudochromosomes: X and Y, and a markedly improved genome annotation compared with the existing assemblies and annotations.
... However, we suggest that this mirrored the rapid and still active spread and diversification of these gene families in tick genomes. Indeed, a considerable presence and activity of mobile genetic elements has been reported in different tick genomes, including the ones we have considered (Gulia-Nuss et al., 2016;Jia et al., 2020), with the I. scapularis genome taken as an example of permissiveness in repeat accumulation (Gulia-Nuss et al., 2016). In this context, DUF1759 is the dispensable Pfam domain with the higher frequencies. ...
... However, we suggest that this mirrored the rapid and still active spread and diversification of these gene families in tick genomes. Indeed, a considerable presence and activity of mobile genetic elements has been reported in different tick genomes, including the ones we have considered (Gulia-Nuss et al., 2016;Jia et al., 2020), with the I. scapularis genome taken as an example of permissiveness in repeat accumulation (Gulia-Nuss et al., 2016). In this context, DUF1759 is the dispensable Pfam domain with the higher frequencies. ...
... Notably, the tick IMD pathway is divergent from what has canonically been described in Drosophila. Ticks and other non-insect arthropods lack genes encoding key mole cules, such as transmembrane peptidoglycan recognition proteins that initiate the IMD pathway, and the signaling molecules IMD and FADD (10,18,19) Instead, the tick IMD pathway responds to multiple cues such as infection-derived lipids that are sensed by the receptor Croquemort (10,11,17) and to cellular stress that is caused by infection (20,21). ...
... ATF4 can also act as a transcrip tional repressor of genes that lead to cell death (30,31). Although the ISR is much less studied in arthropods relative to mammals, genome analysis demonstrates that ticks encode most ISR components with the exception of a PKR ortholog (18,21). We found that B. burgdorferi or A. phagocytophilum infection transcriptionally induced the ISR kinases (PERK, GCN2, and HRI), the eIF2α regulatory molecule, and ATF4 in flat, unfed nymphs ( Fig. 1E through I). ...
A crucial phase in the life cycle of tick-borne pathogens is the time spent colonizing and persisting within the arthropod. Tick immunity is emerging as a key force shaping how transmissible pathogens interact with the vector. How pathogens remain in the tick despite immunological pressure remains unknown. In persistently infected Ixodes scapularis , we found that Borrelia burgdorferi (causative agent of Lyme disease) and Anaplasma phagocytophilum (causative agent of granulocytic anaplasmosis) activate a cellular stress pathway mediated by the endoplasmic reticulum receptor PKR-like ER kinase (PERK) and the central regulatory molecule eIF2α. Disabling the PERK pathway through pharmacological inhibition and RNA interference (RNAi) significantly decreased microbial numbers. In vivo RNAi of the PERK pathway not only reduced the number of A. phagocytophilum and B. burgdorferi colonizing larvae after a bloodmeal but also significantly reduced the number of bacteria that survive the molt. An investigation into PERK pathway-regulated targets revealed that A. phagocytophilum and B. burgdorferi induce activity of the antioxidant response regulator, nuclear factor erythroid 2-related factor 2 (Nrf2). Tick cells deficient for nrf2 expression or PERK signaling showed accumulation of reactive oxygen and nitrogen species in addition to reduced microbial survival. Supplementation with antioxidants rescued the microbicidal phenotype caused by blocking the PERK pathway. Altogether, our study demonstrates that the Ixodes PERK pathway is activated by transmissible microbes and facilitates persistence in the arthropod by potentiating an Nrf2-regulated antioxidant environment.
IMPORTANCE
Recent advances demonstrate that the tick immune system recognizes and limits the pathogens they transmit. Innate immune mediators such as antimicrobial peptides and reactive oxygen/nitrogen species are produced and restrict microbial survival. It is currently unclear how pathogens remain in the tick, despite this immune assault. We found that an antioxidant response controlled by the PERK branch of the unfolded protein response is activated in ticks that are persistently infected with Borrelia burgdorferi (Lyme disease) or Anaplasma phagocytophilum (granulocytic anaplasmosis). The PERK pathway induces the antioxidant response transcription factor, Nrf2, which coordinates a gene network that ultimately neutralizes reactive oxygen and nitrogen species. Interfering with this signaling cascade in ticks causes a significant decline in pathogen numbers. Given that innate immune products can cause collateral damage to host tissues, we speculate that this is an arthropod-driven response aimed at minimizing damage to “self” that also inadvertently benefits the pathogen. Collectively, our findings shed light on the mechanistic push and pull between tick immunity and pathogen persistence within the arthropod vector.
... On the other hand, more recent studies have started to also utilize genetic data from the nuclear genome, results of which highlight differences that were not apparent based on mitochondrial studies alone (Charrier et al., 2019;Jia et al., 2020;Poli et al., 2020). The tick genome has proved complex for genome assembly due to its large size (>2 Gb) and high variability in chromosome structure, resulting in very few published reference genomes (Gulia-Nuss et al., 2016;Cramaro et al., 2017;Jia et al., 2020;De et al., 2023). Even so, nuclear-based genomic studies have shown the ability of these methods to unravel the evolutionary history of even closely related tick species (Jia et al., 2020;Poli et al., 2020), opening up the possibility of studying the taxonomy and identification of other closely related species such as Ixodes ricinus Linnaeus, 1758 and Ixodes inopinatus Estrada-Peña, Petney, Nava, 2014. ...
Ticks are important vectors of human and animal pathogens, but many questions remain unanswered regarding their taxonomy. Molecular sequencing methods have allowed research to start understanding the evolutionary history of even closely related tick species. Ixodes inopinatus is considered a sister species and highly similar to Ixodes ricinus, an important vector of many tick-borne pathogens in Europe, but identification between these species remains ambiguous with disagreement on the geographic extent of I. inopinatus. In 2018-2019, 1583 ticks were collected from breeding great tits (Parus major) in southern Germany, of which 37 were later morphologically identified as I. inopinatus. We aimed to confirm morphological identification using molecular tools. Utilizing two genetic markers (16S rRNA, TROSPA) and whole genome sequencing of specific ticks (n=8), we were able to determine that German samples, morphologically identified as I. inopinatus, genetically represent I. ricinus regardless of previous morphological identification, and most likely are not I. ricinus/I. inopinatus hybrids. Further, our results showed that the entire mitochondrial genome, let alone singular mitochondrial genes (i.e., 16S), is unable to distinguish between I. ricinus and I. inopinatus. Our results suggest that I. inopinatus is geographically isolated as a species (northern Africa and potentially southern Spain and Portugal) and brings into question whether I. inopinatus exists in central Europe. Our results highlight the probable existence of I. inopinatus and the power of utilizing genomic data in answering questions regarding tick taxonomy.
