# Wolbachia infection confers post-translational modification of glutamic acid decarboxylase and other proteins in D. melanogaster

## TL;DR

Wolbachia infection in fruit flies causes changes in brain proteins, including one involved in neurotransmitter production, but these changes don't affect GABA levels or behavior directly.

## Contribution

First description of Wolbachia-induced post-translational modifications in host proteins, revealing a new regulatory mechanism in the host-bacterium relationship.

## Key findings

- Wolbachia infection leads to post-translational modification of multiple proteins in Drosophila, including glutamic acid decarboxylase in the head.
- Infected mated females show improved response to yeast odors, but this is not linked to GABA levels.
- Modifications suggest Wolbachia may alter host proteins to enhance survival in the brain.

## Abstract

Wolbachia pipientis is a ubiquitous intracellular bacterium that is known for its manipulation of reproduction in arthropod hosts. Wolbachia has also been shown to colonize virtually all somatic tissues, including the brain, but little is known about the interaction between host and bacterium in these locations. To this end, we studied the effects of Wolbachia infection on the brain of Drosophila melanogaster. Using comparative proteomics, we uncovered the post-translational modification of many proteins within the Drosophila head and body upon infection, with glutamic acid decarboxylase being modified within the head only. Given this enzyme’s role in neurotransmitter synthesis, we next tested how Wolbachia infection impacts host behaviors and gamma aminobutyric acid (GABA) production within Drosophila. We discovered an improved response to yeast odors in Wolbachia-infected, mated females compared with their uninfected counterparts. Gross measurements of GABA in whole brains showed no detectable change in GABA abundance upon infection. Treatments with a GABA antagonist indicated that the behavioral change was not GABA-dependent, leaving the mechanism behind Wolbachia-mediated changes in behavior obscure. Given the multiple protein changes in the Drosophila head upon infection, we propose a model in which Wolbachia drives the modification of glutamic acid decarboxylase and several metabolic proteins to increase survival in the specialized niche of the brain. These results give rise to new questions about the Wolbachia–Drosophila relationship, and future work will focus on the mechanism through which Wolbachia confers these protein changes.

In order to fully understand the biology of an organism, we must understand its interactions with its resident microbes. Wolbachia is commonly used to study such interactions, but the molecular interactions this bacterium has with its hosts are not well understood, especially within somatic tissues. Here, we address this knowledge gap by characterizing the changes in host proteins within Drosophila melanogaster upon Wolbachia infection. Our results provide the first description of post-translational modifications induced by Wolbachia infection within a host, unveiling a new level of regulation in the Wolbachia–host relationship. The modification of glutamic acid decarboxylase within the Drosophila head was not shown to be connected to changes in GABA production or host behavior, indicating another role for this enzyme during Wolbachia infection within the brain. Altogether, these results provide more information about Wolbachia’s infection of somatic tissue and spark new inquiries into the host–bacterium relationship.