A repertoire of protease inhibitor families in Amblyomma americanum and other tick species: inter-species comparative analyses.
BACKGROUND
Protease inhibitors (PIs) are important regulators of physiology and represent anti-parasitic druggable and vaccine targets. We conducted bioinformatic analyses of genome and transcriptome data to determine the protease inhibitor (PI) repertoire in Amblyomma americanum and in 25 other ixodid tick species. For A. americanum, we compared the PI repertoires in fed and unfed, male and female A. americanum ticks. We also analyzed PI repertoires of female 48, 96 and 120 h-fed midgut (MG) and salivary gland (SG) tissues.


RESULTS
We found 1,595 putative non-redundant PI sequences across 26 ixodid tick species. Ticks express PIs from at least 18 different families: I1, I2, I4, I8, I21, I25, I29, I31, I32, I35, I39, I43, I51, I53, I63, I68, I72 and I74 (MEROPS). The largest PI families were I2, I4 and I8 and lowest in I21, I31, I32, I35 and I68. The majority (75%) of tick PIs putatively inhibit serine proteases, with ~11 and 9% putatively regulating cysteine or metalloprotease-mediated pathways, respectively, and ~4% putatively regulating multiple/mixed protease types. In A. americanum, we found 370 PIs in female and 354 in male ticks. In A. americanum we found 231 and 442 in unfed and fed ticks, respectively. In females, we found 206 and 164 PIs in SG and MG, respectively. The majority of highly cross-tick species conserved PIs were in families I1, I2, I8, I21, I25, I29, I39 and I43.


CONCLUSIONS
Ticks appear to express large and diverse repertoires of PIs that primarily target serine protease-mediated pathways. We speculate that PI families with the highest repertoires may contain functionally redundant members while those with the lowest repertoires are functionally non-redundant PIs. We found some highly conserved PIs in the latter category, which we propose as potential candidates for broad-spectrum anti-tick vaccine candidates or druggable targets in tick control.
Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, 4647 TAMU, College Station, TX, 77843, USA.
Lindsay M
LM
Porter
Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, 4647 TAMU, College Station, TX, 77843, USA.
Željko M
ŽM
Radulović
Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, 4647 TAMU, College Station, TX, 77843, USA. amulenga@cvm.tamu.edu.
Albert
A
Mulenga
D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry* / Q000235:genetics; D005247:Feeding Behavior; D005260:Female; D016678:Genome; D026863:Ixodidae / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000502:physiology; D008297:Male; D011480:Protease Inhibitors / Q000737:chemistry*; D013987:Ticks / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000502:physiology; D059467:Transcriptome
D060829:Arthropod Proteins; D011480:Protease Inhibitors
Amblyomma americanum; Hard ticks; Protease inhibitors in ticks