Molecular and functional characterization of a prostaglandin E2 synthase in the blacklegged tick, Ixodes scapularis Say

Ticks are obligatory ectoparasites that feed exclusively on the blood of vertebrates and often transmit a number of pathogens, resulting in substantial economic loss in the animal industry and presenting risks to human health.  The blacklegged tick, Ixodes scapularis, transmits the most important tick-borne pathogen, Borrelia burgdorferi, the causative agent of Lyme disease.  Tick salivary secretions contain various bioactive components that aid in the manipulation of hosts' defenses.  Ticks secrete large amounts of prostaglandin E2 (PGE2) into the host, where its anti-hemostatic, anti-inflammatory, and immunosuppressive properties facilitate blood feeding.  We hypothesized that ticks possess a PGE2 synthase enzyme, which can be targeted to disrupt tick feeding in the long term.   We have identified and cloned a gene encoding a PGE synthase ortholog (PGES2) in I. scapularis, which is similar to the mammalian PGES2.  The expression pattern and the subcellular localization of PGES2 supports that this gene is expressed in the salivary glands upon blood feeding and constitutively throughout tick feeding.  Examination of PGES2 levels in ticks fed on naive versus immune challenged hosts explores the effects of host acquired immunity to ticks on PGES2 expression in tick salivary glands.  Lastly, we expressed a recombinant tick PGES2 in Escherichia coli to investigate its enzymatic ability to synthesize PGE₂ from PGH₂.  The identification and functional study of PGES2, along with the description of its expression patterns, provides critical information into the biosynthetic pathway of PGE2 in tick salivary glands, and opens the door to future studies into the disruption of tick feeding.