# Rickettsial Influence on Host Membrane Physiology in Arthropod Vectors

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2024 · $471,557

## Abstract

PROJECT SUMMARY
Tick-borne rickettsial diseases (TBRDs) are ubiquitously present throughout the world and case fatality rates in
disease clusters can range up to 100% despite the availability of effective treatment. Thus, there is a need to
increase the “tool box” for TBRD control by supplementing existing strategies with promising novel approaches
that focus on interrupting the Rickettsia transmission cycle in the tick vector. Our recent studies demonstrated
that the non-pathogenic Candidatus Rickettsia andeanae is secreted in tick saliva during feeding, but at a lower
level when compared to pathogenic Rickettsia parkeri, raising questions regarding the underlying mechanisms
that mediate rickettsial pathogenicity. The likelihood that rickettsiae manipulate the arthropod host to enhance
horizontal transmission has been recognized, yet the specific interactions between Rickettsia and ticks remains
unknown. Unfortunately, significant knowledge gaps exist regarding the basic transmission biology of tick-borne
Rickettsia and the specific interactions between Rickettsia and tick physiology that enable transmission, which
represents a significant barrier to the field and has limited the development of novel approaches to control
TBRDs. Thus, the premise of this proposal is that pathogenic Rickettsia, but not non-pathogenic strains of
Rickettsia, alter regulation of tick-derived proteins to enhance salivary gland physiology and increase the
secretory activity of the gland, which facilitates increased horizontal transmission. Salivary gland function is
dependent on strict regulation of acini membrane physiology and thus, we hypothesize that Rickettsia alter
mechanisms for ionic homeostasis to facilitate horizontal transmission. Correspondingly, we hypothesize that
inhibition of ion flux will negate the rickettsial-mediated enhancement of salivary gland activity to prevent tick
bloodmeal feeding and horizontal transmission of Rickettsia. In Specific Aim 1, we will employ a
multidisciplinary approach to measure the influence pathogenic Rickettsia has to secretory activity and
membrane physiology (e.g. membrane potential) of an R. parkeri infected tick salivary gland compared to non-
pathogenic Rickettsia infected ticks. These data will delineate the mechanism by which Rickettsia influences
tick salivary gland physiology to drive pathogenicity. In Specific Aim 2, we will test if dysregulation of K+
homeostasis across salivary gland epithelia will inhibit salivary gland function of rickettsemic ticks to alter blood
feeding biology and reduce R. parkeri virulence in vertebrate disease models. Combined, the experiments
outlined in his proposal will define unique aspects of rickettsial influence on tick physiology that enhance
pathogenicity of Rickettsia, which will assist in resolving the epidemiology of SFG Rickettsia and reveal
intervention points to reduce the health burden of TBRDs.

## Key facts

- **NIH application ID:** 10906370
- **Project number:** 5R01AI153155-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Daniel Swale
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $471,557
- **Award type:** 5
- **Project period:** 2021-08-25 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906370

## Citation

> US National Institutes of Health, RePORTER application 10906370, Rickettsial Influence on Host Membrane Physiology in Arthropod Vectors (5R01AI153155-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10906370. Licensed CC0.

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