Vector-borne diseases affect millions of people worldwide and are becoming an increasing threat as the effects of climate change become more significant. Due to the rise in global temperatures, the likelihood of vector borne diseases will increase in many areas as the range of insects, such as mosquitos, expands and changes. Wolbachia are maternally transmitted bacteria that infect nearly half of the insect species on the planet and block the replication and transmission of several human pathogens within insect vectors (so called ?pathogen blocking?). Wolbachia-infected mosquitos have been released in several parts of the world in order to control the transmission of Dengue virus. Importantly, the mechanism of pathogen blocking is not well understood. Unfortunately, our understanding of the Wolbachia-vector systems have been limited due to the lack of genetic tools in Wolbachia and the intractability of many important vectors. Our project is aimed at overcoming these obstacles by using the model system, Drosophila melanogaster, to identify genetic factors important for the interaction of Wolbachia with its host and SINV, an RNA virus. Our project uses the powerful genetic tools available in the fly to identify host components necessary for Wolbachia pathogen blocking. Our results will define the genetic interaction network for Wolbachia and key host pathways relevant to RNA virus replication, revealing mechanisms used by the bacterium to block pathogens, allowing for precise experimentation in non-model organisms, such as mosquito vectors. Our innovative approach will serve as a platform to mechanistically investigate the Wolbachia-insect- virus tripartite symbioses. The use of a model system allows us to leverage the power of Drosophila genetics to reveal mechanisms of interaction in a previously intractable intracellular symbiont. Results will be broadly relevant to other disease systems, as we will identify pathways and mechanisms for microbe-vector interaction.

Public Health Relevance

Vector-borne diseases affect millions of people worldwide and due to the rise in global temperatures, the likelihood of vector borne diseases will increase in many areas as the range of insects, such as mosquitos, expands and changes. This project focuses on Wolbachia, an intracellular bacterium that blocks pathogen replication and transmission within vectors, and specifically identifies how Wolbachia interact with their insect hosts to achieve this block. Discoveries made as part of this work will be directly applicable to the use of Wolbachia to control disease vectors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI121849-02
Application #
9388949
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2016-12-01
Project End
2018-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Indiana University Bloomington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Bhattacharya, Tamanash; Newton, Irene L G; Hardy, Richard W (2017) Wolbachia elevates host methyltransferase expression to block an RNA virus early during infection. PLoS Pathog 13:e1006427
Bhattacharya, Tamanash; Newton, Irene L G (2017) Mi Casa es Su Casa: how an intracellular symbiont manipulates host biology. Environ Microbiol :