Location: Animal Disease Research
Project Number: 2090-32000-040-014-I
Project Type: Interagency Reimbursable Agreement
Start Date: Jun 1, 2020
End Date: May 31, 2023
1) Demonstrate species specific Babesia sexual stage soluble chemoattractant factor(s) 2) Identify and synthesize soluble chemoattractant factor(s) 3) Confirm migration response to synthesized chemoattractant factor(s)
Babesia bovis and Babesia bigemina are protozoan parasites transmitted by tick vectors that cause significant economic losses to the livestock industry. It is estimated that these two parasites cause annual losses of more than US $10 billion worldwide. Currently, there are no effective vaccines that control bovine babesiosis. The only effective method to minimize significant economic loss to the livestock industry is through the use of acaricides to control tick burdens which consequently reduces transmission of these parasites. However, widespread acaricide use has resulted in the development of acaricide-resistant tick populations. The recent discovery of multiple acaricide-resistant Rhipicephalus tick populations in Mexico raises the concern of tick expansion into Rhipicephalus free areas of the United States. Rhipicephalus ticks are the vectors for B. bovis and B. bigemina. Should an outbreak occur, the US cattle industry's ability to produce food and fiber would be significantly reduced. The life cycle of Babesia parasites is complex and requires infection of mammalian and tick hosts for parasite transmission. Parasites undergo multiple developmental stages that are closely coordinated with tick life cycle events. Within the tick midgut, Babesia parasites transform into sexual stages. We have developed a protocol to induce Babesia sexual stages in in vitro culture. Using supernatants from induced cultures, we have observed species specific migration of gametocyte subpopulations in response to soluble chemoattractant factors. This is the first time that a protozoan parasite sexual stage soluble chemoattractant factor has been observed. To date there is no description in apicomplexan research showing molecules with signaling properties to attract gametes prior to fusion. Understanding how to disrupt extracellular communication between parasite gametes within the tick vector would provide a novel target for transmission blocking vaccine development. Due to our ability to induce sexual stages in in vitro Babesia culture, we are uniquely positioned to study mechanisms of Babesia chemoattraction prior to gamete fusion. Overall Hypothesis: Babesia female gametes release soluble chemoattractant factors that influences the direction of male gamete migration consummating in gamete interaction. The initial development of Babesia in tick midgut is essential for parasite transmission. Within the midgut lumen, Babesia exits from red blood cells and transforms into gametocytes. Babesia male and female gametes fuse to form zygotes. It is unknown if there is signal mechanism to attract male to female gametes for cell fusion. To determine species specific Babesia sexual stage soluble chemoattractant factor(s), in vitro induced Babesia bovis and B. bigemina will be used. Supernatants will be harvested during the in vitro induction of parasites and tested for the presence of chemoattractant (s). Mass spectrometry will be used to identify soluble chemoattractant factor(s). Finally, to confirm the identification of the molecule, chemoattractant factor will be synthesized to demonstrate gamete attraction.