Antibiotics have saved over 200 million lives, but excessive consumption has led to increasingly prevalent resistance. A potential solution is to stop pathogens from invading eukaryotic cells in the first place. This requires a mechanistic understanding of how host-endosymbiont relations are managed. Endosymbiotic Wolbachia bacteria are naturally carried by the well-studied host Drosophila melanogaster, providing an ideal model system for studying the cellular and molecular basis of infection. A 2015 study by Serbus et al. found that when fruit flies were fed dietary yeast, the titer of Wolbachia carried in oogenesis decreased. The molecular mechanisms facilitating this response are not well understood but are thought to be diet-driven insulin signaling. To investigate this further, fruit flies were exposed to nutrients, compounds and small molecule inhibitors to test specific hypotheses related to insulin signaling. The data suggest that the mechanism underlying how dietary yeast suppresses titer is initiated by insulin, and may involve multiple signaling branches. This mechanism requires ingestion of dietary yeast by the insect, allowing yeast-derived factors to trigger somatic insulin release. The oocyte Wolbachia respond to the yeast-enriched host environment through several behavioral and physiological changes. These include decreased bacterial counts, emphasized localization at the posterior pole, and a round nucleoid shape. The data suggest that these outcomes may be due to multiple effectors interacting within the insulin signaling and epidermal growth factor receptor pathways. These findings provide a foundation of knowledge to continue building upon, and ultimately clarify how host-diet manipulates titer, so as to maximize bacterial control.
