Wolbachia are known as intracellular endosymbionts, meaning that they can only survive within the cells of a host organism. Mosquitoes infected with Wolbachia (either naturally or artificially) have dozens or even hundreds of the bacteria in their cells, tinkering with their biology from within.

But how exactly does Wolbachia alter the cell and infect its host? That’s the question that led Professor Irene Newton to create her lab at IU in 2011.

In her February 2023 paper, currently in the process of peer review, Prof. Newton explored the function of a protein secreted by Wolbachia called WalE1. Newton’s previous work had shown that WalE1 wasn’t a typical bacterial protein. It has a sequence of amino acids called a synuclein domain: something that only exists in vertebrates.

Wolbachia itself clearly isn’t a vertebrate and neither are the insects that it infects, yet it still makes a protein with a synuclein domain. As Newton describes it, this seemingly useless sequence is a genius way of interacting with the host cell.

“Bacterial proteins have certain structures and homologies that look like those from eukaryotic cells,” said Newton, “it‘s like having the right wrench to interact with the right bolt.”

WalE1’s synuclein domain allows it to interact with the host cell precisely and without being detected as an invader. It is the wrench that fits perfectly onto the host cell’s bolt. Only one problem: what is its bolt?

To figure out what exactly WalE1 was targeting in the host cell, Newton and research associate MaryAnn Martin modeled a Wolbachia infection in fruit flies.

Fortunately for them, the IU Bloomington Drosophila Stock Center (the world’s largest Drosophila collection, providing genetic strains of fruit flies across the world) is just steps away. “For our research it’s especially great,” said Newton. “Because of the great tool sets and all the resources here at IU, we can use those resources to translate what we find in flies to the mosquito vector.”

To see how much WalE1 disrupts cell function, Newton and Martin used a toxicity test. When fruit flies are healthy, they can survive exposure to silver nitrate. But when the flies’ kidney cells aren’t working correctly, exposure to the chemical will kill them.

The pair found that flies that had the WalE1 protein were more likely to die from silver nitrate exposure, meaning that their kidney cells weren’t working properly. This demonstrates that WalE1 disrupts host cell function once it binds to Past1.

“This is the first time anyone has identified a specific host protein that a Wolbachia effector targets,” noted Newton. It gives researchers in the field a better understanding than ever before of how this important microbe manipulates host biology.

Of course, there are plenty more proteins to discover. As Martin put it: “It is exciting to be contributing new research findings - and somewhat daunting as well, because WalE1 is just one of many effector proteins with host targets, still a lot to learn!”

The pair will continue their work on WalE1 alongside the other 14 members of the Newton Lab. With each new discovery, the lab improves our understanding of Wolbachia and how we can best use it to combat mosquito-borne diseases.