Characterization of anti-hemostatic factors in the argasid, Argas monolakensis: Implications for the evolution of blood-feeding in the soft tick family

Abstract

To date, the only anti-hemostatic factors characterized for softs ticks are for Ornithodoros moubata and Ornithodoros savignyi, ticks that feeds mainly on mammals. This includes thrombin (ornithodorin and savignin), fXa (TAP and fXaI) and platelet aggregation (disagegin and savignygrin) inhibitors that belong to the BPTI-Kunitz protein family. This raises the question on how well anti-hemostatic factors will be conserved in other soft tick genera that feeds on other vertebrates such as birds. We characterized the anti-hemostatic factors from Argas monolakensis, a soft tick that feeds mainly on Californian gulls. The main anti-clotting factor (monobin) is an ortholog of ornithodorin and savignin and shows similar slow tight-binding kinetics. The main anti-platelet activities are apyrase and fibrinogen receptor antagonists (monogrins). The monogrins are orthologs of disagregin and savignygrin and like savignygrin presents the RGD integrin-recognition motif on the BPTI substrate-binding presenting loop. This implies that the anti-hemostatic factors evolved in the ancestral soft tick lineage and has been maintained in soft tick species from two distinct genera with different host preferences. The Argas derived anti-hemostatic factors bind to mammalian targets with affinities similar to that observed for their orthologs in the Ornithodoros genus. This cross-reactivity could have facilitated the switching of soft ticks from avian to mammalian hosts and can explain in part the ability of Argas ticks, to feed on humans, thereby remaining a possible health risk.

The Toxicogenomic Multiverse: Convergent Recruitment of Proteins Into Animal Venoms

“…Chitinase from the posterior salivary gland of the Southern Sand Octopus Octopus kaurna (GenBank accession number EU790591) is quite similar in form to the enzyme present in wasp venom. A highly divergent chitinase was also recently discovered in the hematophagous-feeding secretions of soft tick Argas monolakensis (91). Birds are the primary host for this tick, and hence the biological role of the hematophagous secretion chitinase is also unknown.…”

Comparative sialomics between hard and soft ticks: Implications for the evolution of blood-feeding behavior

“…monolakensis ticks were collected as described (Mans et al, 2007), salivary glands dissected and frozen at À70 1C until use. Glands from unfed and fed (fed to repletion on chickens 4 days prior to dissection) adult females were thawed in RNAlater and cDNA libraries constructed as previously described (Valenzuela et al, 2002b).…”

“…SGE was prepared as described previously (Mans et al, 2007). Briefly, salivary glands were dissected from female ticks in 20 mM Tris-HCl, 0.15 M NaCl, pH 7.4 by tearing the dorsal cuticle and removing the glands with forceps.…”

“…The BPTI/Kunitz family is composed of proteins that exhibit the basic pancreatic trypsin inhibitor fold (Laskowski and Kato, 1980). BPTIlike proteins act as thrombin, fXa and platelet aggregation inhibitors in soft ticks (Waxman et al, 1990;Karczewski et al, 1994;van de Locht et al, 1996;Joubert et al, 1998;Mans et al, 2002bMans et al, , 2007. In hard ticks, BPTI-like proteins inhibit the fVIIa/TF complex (Francischetti et al, 2002(Francischetti et al, , 2004.…”

Evolution of Vertebrate Hemostatic and Inflammatory Control Mechanisms in Blood-Feeding Arthropods

“…It has been proposed that blood-feeding behavior evolved on numerous occasions in Trombidiformes (Astigmata) and Dermanyssina (Mesostigmata) [5][6][7] . Even though all ticks ( ϳ 900 species) are obligate blood feeders, differences in their blood-feeding biology and salivary gland repertoires suggest an independent evolution of hematophagous lifestyles for argasid (soft) and ixodid (hard) ticks [8][9][10][11] .…”