Each year vector-borne diseases afflict millions of people worldwide, impacting health care systems and economic resources. Contributing to the resurgence of many vector-borne diseases is the resistance to antimicrobials, pesticides and insecticides. In order to develop new counter-measures, we must identify new targets that disrupt the transmission cycle for these diseases. This effort is hindered by the lack of genetic tools and resources available to study the microbe-vector interactions. Our project is aimed at overcoming those obstacles by developing a new model system in which to identify genetic factors important for the interaction of Yersinia pestis (causative agent of plague) with its flea vector. Our model system employs Drosophila melanogaster, the fruit fly, as a surrogate for the flea. Drosophila has been used as a model to study innate immunity as wells as a variety of infectious diseases. We will couple the powerful genetic tools available for flies and Y. pestis with high throughput technologies to identify pathways that contribute to colonization of insects. This innovative approach will serve as a platform in future work that will investigate the molecular details of insect colonization using whole organisms, rather than simulative in vitro conditions. Importantly, our model system with its high throughput capabilities has the potential to be adapted to a drug discovery platform in order to identify compounds that disrupt the microbe-vector interaction for plague and other diseases.

Public Health Relevance

Insects serve as transmission vectors for a variety of globally important diseases, but the factors that influence the interaction of microbes with their insect vectors are largely unexplored, in part because of the difficulty in working with natural vectors. n this project, we will implement a new surrogate infection system using the well-established model organism, Drosophila (fruit fly), as a tool to study the interaction of Y. pestis, the causative agent of plague, with its flea vector. In the future, this technology and the knowledge gained from our work can be applied to drug discovery studies that target important pathways for new biocontrol strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI101242-02
Application #
8606396
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mukhopadhyay, Suman
Project Start
2013-02-01
Project End
2015-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Indiana University Bloomington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Earl, Shaun C; Rogers, Miles T; Keen, Jennifer et al. (2015) Resistance to Innate Immunity Contributes to Colonization of the Insect Gut by Yersinia pestis. PLoS One 10:e0133318