# Emerging Flea-Borne Rickettsial Diseases: vector competence and transmission biology

> **NIH NIH R01** · UNIVERSITY OF SOUTH ALABAMA · 2024 · $460,013

## Abstract

Rickettsia felis was originally identified in the United States as a human pathogen in 1991 and is now
associated with human infection in North and South America, Europe, Africa, Asia, and Oceania. Our
ultimate goal for this research is to elucidate the biological and molecular mechanisms that are critical to
rickettsial transmission by fleas in order to better understand the epidemiology of flea-borne rickettsial
diseases and identify novel points of intervention. Recent discoveries including transmission of R. felis in
the absence of a rickettsemic host and the identification of multiple flea-borne rickettsial agents
cocirculating in flea populations have guided the research to determine if sympatric rickettsial agents
circulating in flea populations influence the transmission one another. Additionally, the assembly of the
cat flea genome now allows for investigation of the flea-derived factors that facilitate or prevent Rickettsia
transmission. The experimental focus of this proposal is to delineate horizontal transmission mechanisms
through comparative analyses of coinfections using three distinct rickettsial strains in cat flea transmission
bioassays. The flea-derived molecules associated with the transmission of Rickettsia by flea hosts are not
known. Studies will also employ gene-editing in fleas to identify transmission determinants in a flea
transmission system. Two limiting factors for vector/disease management and the barriers to advancing
the field are the scant knowledge of 1) basic transmission biology of R. felis and other rickettsial
pathogens in the context of coinfections and, 2) the flea-derived determinants of transmission. The need
to overcome these barriers is evident as field collected fleas in areas of flea-borne rickettsioses outbreaks
have multiple rickettsial agents circulating in the vector population and the fleas are known to be vectors
of a number of pathogens, thus providing knowledge with a broad impact. Through completion of the
specific aims outlined in this proposal, these studies will overcome the hurdles by delineating the role of
coinfections in the transmission of R. felis (Specific Aim 1) and through identification of flea-derived
molecules regulated in response to rickettsial infection relates to vector competence (Specific Aim 2).
Thus, this is a multifaceted approach to decipher the vector and pathogen-associated factors essential to
transmission and will provide a platform to examine other flea-borne bacterial pathogens.

## Key facts

- **NIH application ID:** 10906261
- **Project number:** 5R01AI122672-08
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** Kevin R. Macaluso
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $460,013
- **Award type:** 5
- **Project period:** 2015-12-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906261

## Citation

> US National Institutes of Health, RePORTER application 10906261, Emerging Flea-Borne Rickettsial Diseases: vector competence and transmission biology (5R01AI122672-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906261. Licensed CC0.

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