Time-resolved proteomic profile of Amblyomma americanum tick saliva during feeding.

Tae Kwon Kim,Lucas Tirloni,Jolene K Diedrich,John R Yates,Albert Mulenga,James J Moresco,Antônio F M Pinto,Itabajara Da Silva Vaz,Rhoel Ramos Dinglasan

doi:10.1371/journal.pntd.0007758

Abstract

Amblyomma americanum ticks transmit more than a third of human tick-borne disease (TBD) agents in the United States. Tick saliva proteins are critical to success of ticks as vectors of TBD agents, and thus might serve as targets in tick antigen-based vaccines to prevent TBD infections. We describe a systems biology approach to identify, by LC-MS/MS, saliva proteins (tick = 1182, rabbit = 335) that A. americanum ticks likely inject into the host every 24 h during the first 8 days of feeding, and towards the end of feeding. Searching against entries in GenBank grouped tick and rabbit proteins into 27 and 25 functional categories. Aside from housekeeping-like proteins, majority of tick saliva proteins belong to the tick-specific (no homology to non-tick organisms: 32%), protease inhibitors (13%), proteases (8%), glycine-rich proteins (6%) and lipocalins (4%) categories. Global secretion dynamics analysis suggests that majority (74%) of proteins in this study are associated with regulating initial tick feeding functions and transmission of pathogens as they are secreted within 24–48 h of tick attachment. Comparative analysis of the A. americanum tick saliva proteome to five other tick saliva proteomes identified 284 conserved tick saliva proteins: we speculate that these regulate critical tick feeding functions and might serve as tick vaccine antigens. We discuss our findings in the context of understanding A. americanum tick feeding physiology as a means through which we can find effective targets for a vaccine against tick feeding.

Highlights

Ticks and tick-borne diseases (TBDs) have been on the rise and have greatly impacted human and veterinary medicine
In early feeding stages (24–72 h), A. americanum tick saliva was observed as a white flake that accumulated on the mouthparts over time and was collected every 15–30 min for 4 h by washing the mouthparts with sterile phosphate buffered saline
We have previously shown that RNAi-mediated silencing of A. americanum tick saliva serpin 19, an anti-coagulant, [73], which is conserved in I. scapularis ticks [42, 65], caused significant mortality demonstrating the importance of this protein in tick physiology

Summary

Introduction

Ticks and tick-borne diseases (TBDs) have been on the rise and have greatly impacted human and veterinary medicine. Ticks have gained the attention in public health policy with a recent publication that advocated for One Health solutions listing 17 human TBDs among sources of human health concerns [1]. The dramatic rise related to ticks and TBDs have caught the attention of United States (US) lawmakers, as shown in the 21st Century Cures Act of 2016, which created the TBD Working Group. Under the Cures Act, the TBD Working Group was tasked with evaluating the impact of TBDs and required research to find solutions (https:// www.hhs.gov/ash/advisory-committees/tickbornedisease/index.html). Six of the 23 human vector-borne diseases that are listed by the World Health Organization are tick-borne that include Crimean-Congo haemorrhagic fever, Lyme disease, relapsing fever, rickettsial diseases (spotted fever and Q fever), tick-borne encephalitis, and tularemia (http://www.who.int/ news-room/fact-sheets/detail/vector-borne-diseases). In the US, Amblyomma americanum, the lone star tick is among one of the tick species of medical and veterinary health significance

Objectives

Methods

Results

Conclusion