<i>Wolbachia</i> infection confers post-translational modification of glutamic acid decarboxylase and other proteins in <i>D. melanogaster</i>

<i>Wolbachia pipientis</i> is a ubiquitous intracellular bacterium that is known for its manipulation of reproduction in arthropod hosts. <i>Wolbachia</i> 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 <i>Wolbachia</i> infection on the brain of <i>Drosophila melanogaster</i>. Using comparative proteomics, we uncovered the post-translational modification of many proteins within the <i>Drosophila</i> 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 <i>Wolbachia</i> infection impacts host behaviors and gamma aminobutyric acid (GABA) production within <i>Drosophila</i>. We discovered an improved response to yeast odors in <i>Wolbachia</i>-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 <i>Wolbachia</i>-mediated changes in behavior obscure. Given the multiple protein changes in the <i>Drosophila</i> head upon infection, we propose a model in which <i>Wolbachia</i> 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 <i>Wolbachia-Drosophila</i> relationship, and future work will focus on the mechanism through which <i>Wolbachia</i> confers these protein changes.IMPORTANCEIn order to fully understand the biology of an organism, we must understand its interactions with its resident microbes. <i>Wolbachia</i> 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 <i>Drosophila melanogaster</i> upon <i>Wolbachia</i> infection. Our results provide the first description of post-translational modifications induced by <i>Wolbachia</i> infection within a host, unveiling a new level of regulation in the <i>Wolbachia</i>-host relationship. The modification of glutamic acid decarboxylase within the <i>Drosophila</i> head was not shown to be connected to changes in GABA production or host behavior, indicating another role for this enzyme during <i>Wolbachia</i> infection within the brain. Altogether, these results provide more information about <i>Wolbachia</i>'s infection of somatic tissue and spark new inquiries into the host-bacterium relationship.