# The mechanistic basis of how symbionts assist vector control

> **NIH NIH F32** · VANDERBILT UNIVERSITY · 2020 · $65,310

## Abstract

Project Summary:
 The World Health Organization recently recommended the deployment of Wolbachia-infected
mosquitoes for pilot biocontrol efforts that curb the transmission of Zika and dengue viruses to humans. This
recommendation is based principally on two facets of Wolbachia biology. First, these maternally-transmitted,
endosymbiotic bacteria cause pathogen blocking by altering the competency of mosquitoes to serve as
effective hosts for viral replication. Second, Wolbachia alter sperm and egg via a process termed cytoplasmic
incompatibility (CI) that is used for population suppression (reduction in mosquito population size) and
population replacement (spread of pathogen-blocking Wolbachia into an uninfected population) strategies.
Specifically, CI results in embryonic lethality when an infected male mates with an uninfected female. The
modified sperm fertilize the uninfected egg, however post-fertilization defects ensue spanning failed replication
of paternal DNA, delayed breakdown of paternal nuclear envelope and cell cycle activation, and a failure of
segregation of paternal chromosomes. Importantly, the pre-fertilization modifications of sperm remain
enigmatic, namely how Wolbachia in the testes express and use the toxin gene products of cytoplasmic
incompatibility factors (cif) A and B to establish the onset of CI. As these two gene products represent a
breakthrough in the understanding of CI, the central hypothesis of the proposed research is that prophage WO
genes, cifA and cifB, encode protein products that escape the Wolbachia membrane in testes to interact with
eukaryotic host ligands, ultimately modifying sperm integrity to cause CI. In Aim 1, I will use DNA cytochemistry
and enzymatic assays to determine the types of sperm modifications inflicted by the Cif proteins in vivo. In Aim
2, I will investigate localization patterns and potential ligands to test the presumption that viral particles
transport the proteins to interact with sperm nuclear DNA. Examinations thus far have yet to yield any
mechanistic advance for the initial CI defects, and the rising interest in deploying Wolbachia to curb arbovirus
transmission necessitates an explanation of Wolbachia's drive system. If successful, this research will pioneer
mechanistic studies of Wolbachia-induced reproductive parasitism, inform Wolbachia's efficacy and delivery as
a tool to control diverse zoonotic diseases, and provide multiple lines of evidence for the discovery of the
biochemical basis of CI.

## Key facts

- **NIH application ID:** 9893705
- **Project number:** 5F32AI140694-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Brittany Leigh
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893705

## Citation

> US National Institutes of Health, RePORTER application 9893705, The mechanistic basis of how symbionts assist vector control (5F32AI140694-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9893705. Licensed CC0.

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