The intracellular symbiont alters development and metabolism to buffer against nutritional stress.

Unlabelled: The intracellular bacterium is a common symbiont of many arthropods and nematodes, well studied for its impacts on host reproductive biology. However, its broad success as a vertically transmitted infection cannot be attributed to manipulations of host reproduction alone. Using the model and their natively associated strain " Mel", we show that infection supports fly development and buffers against nutritional stress. infection across several fly genotypes and a range of nutrient conditions resulted in reduced pupal mortality, increased adult emergence, and larger size. We determined that the exogenous supplementation of pyrimidines partially rescued developmental phenotypes in the -free flies, and that titers were responsive to reduced gene expression of the fly's pyrimidine synthesis pathway. In parallel, transcriptomic and metabolomic analyses indicated that impacts larval biology far beyond pyrimidine metabolism. -infected larvae had strong signatures of shifts in glutathione and mitochondrial metabolism, plus significant changes in the expression of key developmental regulators including , the insulin receptor ( ), and the juvenile hormone receptor ( ). We propose that acts as a beneficial symbiont to support fly development and enhance host fitness, especially during periods of nutrient stress.

Significance: is a bacterial symbiont of arthropods and nematodes, well described for its manipulations of arthropod reproduction. However, many have theorized there must be more to this symbiosis, even in well-studied host relationships such as with . Reproductive impacts alone cannot explain the success and ubiquity of this bacterium. Here, we use and their native infections to show that supports fly development and significantly buffers flies against nutritional stress. These developmental advantages might help explain the ubiquity of infections.