Selective cysteine protease inhibition contributes to blood-feeding success of the tick Ixodes scapularis.
Ixodes scapularis is the main vector of Lyme disease in the eastern and central United States. Tick salivary secretion has been shown as important for both blood-meal completion and pathogen transmission. Here we report a duplication event of cystatin genes in its genome that results in a transcription-regulated boost of saliva inhibitory activity against a conserved and relatively limited number of vertebrate papain-like cysteine proteases during blood feeding. We further show that the polypeptide products of the two genes differ in their binding affinity for some enzyme targets, and they display different antigenicity. Moreover, our reverse genetic approach employing RNA interference uncovered a crucial mediation in tick-feeding success. Given the role of the targeted enzymes in vertebrate immunity, we also show that host immunomodulation is implicated in the deleterious phenotype of silenced ticks making I. scapularis cystatins attractive targets for development of anti-tick vaccines.
Kotsyfakis
Michalis
M
Vector Biology Section, Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, Maryland 20852, USA.
Karim
Shahid
S
Andersen
John F
JF
Mather
Thomas N
TN
Ribeiro
José M C
JM
D000818:Animals; D019295:Computational Biology / Q000379:methods; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005821:Genetic Techniques; D006801:Humans; D018884:Ixodes; D008193:Lyme Disease / Q000517:prevention & control; D008297:Male; D051379:Mice; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D011817:Rabbits; D013987:Ticks
D015853:Cysteine Proteinase Inhibitors; D012330:RNA, Double-Stranded; D003546:Cysteine Endopeptidases