Research Systems: Wolbachia-Drosophila Symbioses

Wolbachia-Drosophila associations: powerful model systems for understanding the cellular mechanisms underlying host-symbiont interactions

“Our darkest fiction is full of Orwellian dystopias, shadowy cabals, and mind-controlling supervillains. But it turns out that the brainless, microscopic, single-celled organisms that live inside us have been pulling on our strings all along.”
― Ed Yong, I Contain Multitudes: The Microbes Within Us and a Grander View of Life

Using the powerful Wolbachia-Drosophila system, we have shown that Wolbachia competes poorly with its host for intracellular transport, likely preventing the bacteria from inhibiting vital host processes. In cell culture, we have shown that Wolbachia is capable of rapidly exiting infected host cells and entering uninfected host cells within hours of exposure (see Publications). Current work uses these systems, which we describe below, to investigate how Wolbachia interacts with host motor proteins, controls host cell differentiation, and subverts host defenses during cell-to-cell transfer.

Uninfected and wMel Wolbachia-infected Drosophila melanogaster grown in vials in the lab — Uninfected and wMel *Wolbachia*-infected *Drosophila melanogaster* grown in vials in the lab

Wolbachia-infected Drosophila melanogaster oocyte overexpressing the host motor protein Kinesin Heavy Chain, causing excess Wolbachia to accumulate at the posterior pole — *Wolbachia*-infected *Drosophila melanogaster* oocyte overexpressing the host motor protein Kinesin Heavy Chain, causing excess *Wolbachia* to accumulate at the posterior pole

JW18 Drosophila melanogaster cell line infected with the wMel strain of Wolbachia — JW18 *Drosophila melanogaster* cell line infected with the wMel strain of *Wolbachia*

Immortalizing cell culture I made from Drosophila willistoni embryos infected with the wWil strain of Wolbachia — Immortalizing cell culture S. Russell made from *Drosophila willistoni* embryos infected with the wWil strain of *Wolbachia*

Wolbachia’s applications in insect disease vector control

Three aspects of Wolbachia’s biology make it relevant to controlling transmissible human diseases:

Wolbachia association reduces the transmission rate of certain viruses (e.g., Dengue, Zika, and Chikungunya) from mosquitoes to humans
In insects, Wolbachia-induced reproductive manipulations such as cytoplasmic incompatibility can be used to either:
- Spread Wolbachia infection through the population (to spread viral protection)
- Induce sterility in the population through incompatible matings (termed the sterile male technique), therefore reducing insect population sizes
In filarial nematodes, Wolbachia is necessary for host survival and reproduction, providing a non-eukaryotic drug target for patient treatment

Cytoplasmic incompatibility prevents infected males from producing viable progeny with uninfected females. The box in the upper right diagrams the outcome of crosses between infected (filled circles) and uninfected (empty circles) males and females (green check = viable; red X = inviable). Cytoplasmic incompatibility delays the male pronucleus during the first mitosis, resulting in substantial embryonic mortality at this stage.

Our work on the molecular mechanisms enabling Wolbachia’s different transmission strategies will be directly applicable to the use of this bacterium as a biological control agent in the following ways:

Once we know what genes and mechanisms Wolbachia uses to transmit itself through the female germline, we will be able to select or engineer strains for more efficient inheritance.
Similarly, when we understand how Wolbachia accomplishes cell-to-cell transmission, and how this relates to its ability to horizontally transmit between hosts, we will select or engineer strains that have limited capability for horizontal transmission.