Defining the molecular mechanisms driving transovarial transmission of Acari-borne pathogens using the Borrelia turicatae-Ornithodoros turicata model.

About This Grant

Project Summary Acari (mite and tick)-borne illnesses severely impact human health, and it is essential to understand the mechanisms maintaining the pathogens within their vectors for the development of countermeasures. Transovarial transmission (ToT) is used by mites and ticks to keep vector populations persistently colonized, but virtually nothing is known about the mechanisms of vertical transmission. While most work focuses on ixodid ticks, mites and argasids are understudied vectors most likely because of their complex biology. We developed the argasid–relapsing fever (RF) spirochete model (Ornithodoros turicata–Borrelia turicatae), which is one of the most comprehensive systems to study reproduction and ToT. We reported O. turicata vertically transmits B. turicatae by autogenous reproduction (laying of eggs without a blood meal), a unique aspect of argasid reproduction. This means that endemic foci of RF spirochete-infected ticks can be established quickly without needing a blood meal host. We have also identified an isolate of B. turicatae that is infectious by tick bite but fails to be vertically transmitted to offspring ticks. This phenotype enables us to study the mechanisms of ToT in this complex non-model system through comparative genomics. Also, our work in O. turicata genomics identified vitellogenins and the vitellogenin receptor, proteins that can be targeted by plant and veterinary microbial pathogens for ToT. Building on prior work and our developed entomological, bacterial, genomics, and genetics resources, we can now identify the molecular players involved in ToT. This application implements a functional genomics approach to test the hypothesis that ToT of RF Borrelia occurs throughout the reproductive cycles of female ticks and is driven by B. turicatae binding to vitellogenins and/or the vitellogenin receptor. The first aim will define the reproductive cycles of O. turicata and assess the dynamics of ToT for B. turicatae. This will be accomplished through the utilization of developed in vitro and in vivo tick feeding systems, tick colonies, and a diverse collection of B. turicatae isolates. The second aim will identify the molecular constituents of ToT. We identified gene loci and plasmids associated with a vertical transmission phenotype. We will build on these findings through comparative genomics and transcriptomics and identify B. turicatae surface proteins that bind to vitellogenins and/or the vitellogenin receptor. Using our developed genetics, we will transform the non- vertically transmitted B. turicatae isolate with plasmid and/or gene candidates to restore a ToT phenotype. While rickettsial, viral, parasitic, and RF Borrelia undergo ToT in mites and ticks, the molecular mechanisms are unknown. The completion of this project will result in the first identification of the molecular constituents involved with ToT of an Acari-borne pathogen. These findings will likely be broadly applicable and move the field closer to finding interventions that disrupt the life cycle of pathogen and vector.