# Identifying Wolbachia effectors that facilitate host infection

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $386,406

## Abstract

PROJECT SUMMARY/ABSTRACT
Wolbachia pipientis is an obligate intracellular alpha-proteobacterium that infects 40-60% of insect species on
the planet. Wolbachia infection inhibits RNA virus replication in insects, a phenomenon known as pathogen
blocking. Therefore, Wolbachia infected mosquitos are being released in many parts of the world to control the
spread of human diseases. Importantly, although the mechanism behind Wolbachia’s virus inhibition is not
known, Wolbachia must colonize the host and be efficiently maternally transmitted in order for pathogen
blocking to work. Our long-term goals are to identify the mechanisms used by Wolbachia to establish infection.
To that end, we focus on the type IV secretion system (T4SS), a molecular nanomachine used by Wolbachia to
inject proteins, termed effectors, into the host cellular environment. Via these secreted effectors, the host cell is
modified, allowing Wolbachia to invade and persist.
Our previous work identified and characterized the first secreted effector in Wolbachia (WalE1) and established
that this effector disrupts host endocytosis. We developed a live assay for visualizing Wolbachia infection and
showed that the actin cytoskeleton must be intact for this to occur. We identified important Wolbachia effectors
upregulated during infection using proteomics and show that the T4SS is upregulated upon host internalization.
In this proposed renewal, we will continue or work to identify the Wolbachia secretome across strains, within
both Drosophila and Aedes, and identify pathways important for Wolbachia infection of both host species. We
will also further identify how the important effector WalE1 functions across strains and determine the
conservation and function of important domains for this protein. Guided by strong preliminary data, we propose
to pursue three Specific Aims to identify and characterize Wolbachia effectors, host pathways important for
infection by the microbe, and WalE1 function. We will (1) Determine and characterize the Wolbachia
secretome, across strains, (2) Identify host pathways important for colonization of hosts by different
Wolbachia strains, and (3) Characterize the molecular biology and evolution of Wolbachia’s WalE1.
Studies of Wolbachia - host interactions are still in their infancy despite the recognized contributions of
endosymbiotic associations to insect reproduction and evolution, and the ability to alter vector competence.
These proposed studies will significantly advance our understanding of how Wolbachia employs its effectors to
establish infection, a necessary prerequisite to pathogen blocking.

## Key facts

- **NIH application ID:** 10818862
- **Project number:** 2R01AI144430-06
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Irene Newton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $386,406
- **Award type:** 2
- **Project period:** 2019-05-10 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818862

## Citation

> US National Institutes of Health, RePORTER application 10818862, Identifying Wolbachia effectors that facilitate host infection (2R01AI144430-06). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10818862. Licensed CC0.

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