A snapshot of the Ixodes scapularis degradome

Mulenga, Albert; Erikson, Kelly

doi:10.1016/j.gene.2011.04.008

Cited by 23 publications

(39 citation statements)

References 128 publications

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“…At the time of this study, protease families that were encoded by A. americanum were not enumerated, presumably because its genome had not been sequenced. However, analysis of annotated sequences from I. scapularis showed that the tick might encode for all protease categories: aspartic, cysteine, serine, metallo-, and threonine proteases (79). Here, we found that A. americanum secretes at least 94 proteases in saliva during feeding.…”

Section: Resultsmentioning

confidence: 99%

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Kim

Tirloni

Pinto

et al. 2019

Preprint

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24Amblyomma americanum ticks transmit more than a third of human tick-borne disease 25 (TBD) agents in the United States. Tick saliva proteins are critical to success of ticks as vectors 26 of TBD agents, and thus might serve as targets in tick antigen-based vaccines to prevent TBD 27 infections. We describe a systems biology approach to identify, by LC-MS/MS, saliva proteins 28 (tick=1182, rabbit=335) that A. americanum ticks likely inject into the host every 24 h during the 29 first 8 days of feeding, and towards the end of feeding using two different sample preparation 30 approaches (in-gel and in-solution). The in-gel approach determined molecular identification of 31 predominant protein bands in tick saliva, and the in-solution added depth to discovery of 32 proteins. Searching against entries in GenBank grouped tick and rabbit proteins in this study into 33 27 and 25 functional categories. Aside from housekeeping-like proteins, majority of tick saliva 34 proteins belong to the tick-specific (no homology to non-tick organisms: 32%), protease 35 inhibitors (13%), proteases (8%), glycine-rich proteins (6%) and lipocalins (4%) categories.36 Global secretion dynamics analysis suggests that majority (74%) of proteins in this study are 37 associated with regulating initial tick feeding functions and transmission of pathogens as they are 38 secreted within 24-48 h of tick attachment. Comparative analysis of the A. americanum tick 39 saliva proteome to five other tick saliva proteomes identified 284 conserved tick saliva proteins:40 we speculate that these regulate critical tick feeding functions and might serve as tick vaccine 41 antigens. We discuss our findings in the context of understanding A. americanum tick feeding 42 physiology as a means through which we can find effective targets for a vaccine against tick 43 feeding. 44 45 3 46 Author Summary 47The lone star tick, Amblyomma americanum, is a medically important species in US that 48 transmits 5 of the 16 reported tick-borne disease agents. Most recently, bites of this tick were 49 associated with red meat allergies in humans. Vaccination of animals against tick feeding has 50 been shown to be a sustainable and effective alternative to current acaricide based tick control 51 method which has several limitations. The pre-requisite to tick vaccine development is to 52 understand the molecular basis of tick feeding physiology. Toward this goal, this study has 53 identified proteins that A. americanum ticks inject into the host at different phases of its feeding 54 cycle. This data set has identified proteins that A. americanum inject into the host within 24-48 h 55 of feeding before it starts to transmit pathogens. Of high importance, we identified 284 proteins 56 that are present in saliva of other tick species, which we suspect regulate important role(s) in tick 57 feeding success and might represent rich source target antigens for a tick vaccine. Overall, this 58 study provides a foundation to understand the molecular mechanisms regulating tick feeding 59 p...

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Section: Resultsmentioning

confidence: 99%

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Kim

Tirloni

Pinto

et al. 2019

Preprint

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“…Ticks used in validation of RNAi silencing were sampled at 48 h to ensure that the ticks were alive and could attempt to feed. Tick actin PCR primers (Mulenga et al, 2009) were used as an internal control.…”

Section: Methodsmentioning

confidence: 99%

Deorphanization and target validation of cross-tick species conserved novel Amblyomma americanum tick saliva protein

Mulenga

Kim

Ibelli

2013

International Journal for Parasitology

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We previously identified a cross-tick species conserved tick feeding stimuli responsive Amblyomma americanum (Aam) AV422 gene. This study demonstrates that AamAV422 belongs to a novel group of arthropod proteins that is characterized by 14 cysteine amino acid residues: C23-X7/9-C33-X23/24-C58-C8-C67X7-X75-X23-C99-X15-C115-X10-C126X24/25/33-C150C151-X7-C159-X8-X168-X23/24-C192-X9/10-C202 predicted to form seven disulfide bonds. We show that AamAV422 protein is a ubiquitously expressed protein that is injected into the host within the first 24 h of the tick attaching onto the host as revealed by western blotting analyses of recombinant (r)AamAV422, tick saliva and dissected tick organ protein extracts using antibodies to 24 h and 48 h tick saliva proteins (TSPs). Native AamAV422 is apparently involved with mediating tick anti-hemostasis and anti-complement functions in that rAamAV422 delayed plasma clotting time in a dose responsive manner by up to ~160 s, prevented platelet aggregation by up to ~16% and caused ~24% reduction in production of terminal complement complexes. Target validation analysis revealed that rAamAV422 is a potential candidate for a cocktail or multivalent tick vaccine preparation in that RNA interference (RNAi)-mediated silencing of AamAV422 mRNA caused a statistically significant (~44%) reduction in tick engorgement weights, which is proxy for amounts of ingested blood. We speculate that AamAV422 is a potential target antigen for development of the highly desired universal tick vaccine in that consistent with high conservation among ticks, antibodies to 24 h Ixodes scapularis TSPs specifically bound rAamAV422. We discuss data in this study in the context of advancing the biology of tick feeding physiology and discovery of potential target antigens for tick vaccine development.

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“…Most of the proteases here are likely associated with tick feeding regulation in that 75% (25/33) were detected between 24-120 h during tick feeding except for seven that were identified only in SD (S2 Table). Nearly 40% of proteases in the I. scapularis genome are metalloproteases [68]. Whether or not the observation in this study that majority of proteases in I. scapularis tick saliva are metalloproteases reflects the protease composition in I. scapularis genome or it is a physiological event, is unknown at this point.…”

Section: Majority Of Proteases In I Scapularis Saliva Are Metallopromentioning

confidence: 74%

Ixodes scapularistick saliva proteins sequentially secreted every 24h during blood feeding

Kim¹

2016

2016 International Congress of Entomology

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Ixodes scapularis is the most medically important tick species and transmits five of the 14 reportable human tick borne disease (TBD) agents in the USA. This study describes LC-MS/MS identification of 582 tick-and 83 rabbit proteins in saliva of I. scapularis ticks that fed for 24,48,72,96, and 120 h, as well as engorged but not detached (BD), and spontaneously detached (SD). The 582 tick proteins include proteases (5.7%), protease inhibitors (7.4%), unknown function proteins (22%), immunity/antimicrobial (2.6%), lipocalin (3.1%), heme/iron binding (2.6%), extracellular matrix/ cell adhesion (2.2%), oxidant metabolism/ detoxification (6%), transporter/ receptor related (3.2%), cytoskeletal (5.5%), and housekeeping-like (39.7%). Notable observations include: (i) tick saliva proteins of unknown function accounting for >33% of total protein content, (ii) 79% of proteases are metalloproteases, (iii) 13% (76/582) of proteins in this study were found in saliva of other tick species and, (iv) ticks apparently selectively inject functionally similar but unique proteins every 24 h, which we speculate is the tick's antigenic variation equivalent strategy to protect important tick feeding functions from host immune system. The host immune responses to proteins present in 24 h I. scapularis saliva will not be effective at later feeding stages. Rabbit proteins identified in our study suggest the tick's strategic use of host proteins to modulate the feeding site. Notably fibrinogen, which is central to blood clotting and wound healing, was detected in high abundance in BD and SD saliva, when the tick is preparing to terminate feeding and detach from the host. A remarkable tick adaptation is that the feeding lesion is completely healed when the tick detaches from the host. Does the tick concentrate fibrinogen at the feeding site to aide in promoting healing of the feeding lesion? Overall, these data provide broad insight into molecular mechanisms regulating different tick feeding phases. These data set the foundation for in depth I. scapularis tick feeding physiology and TBD transmission studies.PLOS Neglected Tropical Diseases |

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A snapshot of the Ixodes scapularis degradome

Cited by 23 publications

References 128 publications

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Time-resolved proteomic profile ofAmblyomma americanumtick saliva during feeding

Deorphanization and target validation of cross-tick species conserved novel Amblyomma americanum tick saliva protein

Ixodes scapularistick saliva proteins sequentially secreted every 24h during blood feeding

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