Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

<--Please Select Department-->

First Advisor's Name

Laura Serbus

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Matthew DeGennaro

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Mauricio Rodriguez-Lanetty

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Jamie Theobald

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

Yuk-Ching Tse-Dinh

Fifth Advisor's Committee Title

Committee member

Keywords

Wolbachia, Drosophila, Density/Titer, Host mechanisms, Absolute qPCR

Date of Defense

3-23-2021

Abstract

Wolbachia pipientis is one of the most widespread bacterial endosymbionts, infecting mites, crustaceans, and filarial nematodes as well as about half of all insect species. These bacteria cause many neglected human diseases that include African river blindness and lymphatic filariasis affecting over 100 million people worldwide. Interestingly, Wolbachia also suppress the transmission of viruses such as Dengue, Chikungunya, and Zika. In most reported cases, Wolbachia antiviral activity is a density-dependent effect, with high Wolbachia density conferring the strongest viral suppression. However, little is currently known about how Wolbachia load is controlled within the insect host. A small number of studies have suggested that germline Wolbachia abundance is responsive to host dietary signaling and other factors. It remains an open question whether the germline mechanisms that affect Wolbachia colonization are also shared by the soma. The work of my dissertation focuses on identifying the cellular and molecular mechanisms that affect the abundance of Wolbachia carried within the insect host. To that end, we have optimized a whole body qPCR screening assay to facilitate identification of candidate pathways. Employing this technique, we have demonstrated that host diet affects Wolbachia abundance in reproductive tissues, but not whole body Wolbachia loads. To identify more generalized mechanisms that affect Wolbachia load, we tested candidate cellular pathways for their impact on body-wide Wolbachia abundance. The analysis revealed 5 candidate host processes as major regulators of Wolbachia abundance in D. melanogaster and D. simulans hosts. Inhibition of the ubiquitin-proteasome pathway decreased body-wide Wolbachia loads, whereas, inhibition of the IMD pathway, Calcium signaling, the Ras/mTOR pathway, and Wnt signaling increased body-wide loads. Genetic manipulation further confirmed the impact of Ras/mTOR and Wnt pathways on Wolbachia load in vivo. Taken together, these findings provide new insight into how bacterial endosymbiont loads are specified by the host.

Identifier

FIDC009683

Previously Published In

Christensen S, Camacho M, Sharmin Z, Momtaz AJMZ, Perez L, Navarro G, Triana J, Samarah H, Turelli M, Serbus LR. Quantitative methods for assessing local and bodywide contributions to Wolbachia titer in maternal germline cells of Drosophila. BMC Microbiol. 2019 Sep 3;19(1):206. doi: 10.1186/s12866-019-1579-3. PMID: 31481018; PMCID: PMC6724367.

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Available for download on Tuesday, April 18, 2023

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