Peptidase inhibitors in tick physiology

Abstract

Abstract. Peptidase inhibitors regulate a wide range of physiological processes involved in the interaction between hematophagous parasites and their hosts, including tissue remodeling, the immune response and blood coagulation. In tick physiology, peptidase inhibitors have a crucial role in adaptation to improve parasitism mechanisms, facilitating blood feeding by interfering with defense-related host peptidases. Recently, a larger number of studies on this topic led to the description of several new tick inhibitors displaying interesting novel features, for example a role in pathogen transmission to the host. A comprehensive review discussing these emerging concepts can therefore shed light on peptidase inhibitor functions, their relevance to tick physiology and their potential applications. Here, we summarize and examine the general characteristics, functional diversity and action of tick peptidase inhibitors with known physiological roles in the tick−host−pathogen interaction.

A physiologic overview of the organ-specific transcriptome of the cattle tick Rhipicephalus microplus

“…Noticeably, although several inhibitors of cysteine proteinase (cystatins) were identified, these were nearly ten times less expressed than inhibitors of serine proteases. These inhibitors can be related to the inhibition of mammalian proteases involved in blood coagulation and complement cascades 87 , acting as a regulator of blood 88 and modulation of the tick immune proteolytic cascades, that have been ascribed relevant roles in the interaction with the microbiota and with pathogens 89 . However, it is also possible to speculate that part of these inhibitors might be negative regulators of hemoglobin degradation, as the proteolytic activity involves the release of large amounts of heme, a pro-oxidant molecule 90 .…”

Modeling Novel Putative Drugs and Vaccine Candidates against Tick-Borne Pathogens: A Subtractive Proteomics Approach

“…Comparatively, it was evident from previous reports that outer membrane proteins are vaccine candidates and that cytoplasmic proteins are drug targets [ 21 , 109 ]. It is well known that exported proteins are the prominent molecules of interaction with cells infected by pathogens; therefore, they are potential candidates for vaccine targets [ 110 , 111 , 112 , 113 , 114 ]. The antigenicity and allergenicity analysis of target proteins revealed that eight among them were antigenic while the remaining four proteins were non-antigenic and all the target proteins were non-allergen ( Table 2 ).…”

The Use of Tick Salivary Proteins as Novel Therapeutics

“…Serine protease inhibitors form four groups – Kunitz-domain inhibitors, serpins, trypsin inhibitor-like cysteine-rich domain inhibitors (TIL-domain inhibitors), and Kazal-domain inhibitors – while the cysteine protease inhibitors usually belong to the cystatin family. Tick protease inhibitors and their functions are reviewed elsewhere (Schwarz et al, 2012; Blisnick et al, 2017; Porter et al, 2017; Parizi et al, 2018), and the therapeutic potential of serpins and cystatins was outlined in our previous review (Chmelar et al, 2017). Here we discuss the therapeutic potential of the other two groups, Kunitz- and TIL-domain inhibitors.…”