Recent declines in the health of the honey bee have startled researchers and lay people alike as honey bees are agriculture’s most important pollinator. Honey bees are important pollinators of many major crops and add billions of dollars annually to the US economy through their services. One factor that may influence colony health is the microbial community. Indeed, the honey bee worker digestive tract harbors a characteristic community of bee-specific microbes, and the composition of this community is known to impact honey bee health. However, the honey bee is a superorganism, a colony of eusocial insects with overlapping generations where nestmates cooperate, building a hive, gathering and storing food, and raising brood. In contrast to what is known regarding the honey bee worker gut microbiome, less is known of the microbes associated with developing brood, with food stores, and with the rest of the built hive environment. More recently, the microbe Bombella apis was identified as associated with nectar, with developing larvae, and with honey bee queens. This bacterium is related to flower-associated microbes such as Saccharibacter floricola and other species in the genus Saccharibacter, and initial phylogenetic analyses placed it as sister to these environmental bacteria. Here, we used comparative genomics of multiple honey bee-associated strains and the nectar-associated Saccharibacter to identify genomic changes that may be associated with the ecological transition to honey bee association. We identified several genomic differences in the honey bee-associated strains, including a complete CRISPR/Cas system. Many of the changes we note here are predicted to confer upon Bombella the ability to survive in royal jelly and defend themselves against mobile elements, including phages. Our results are a first step towards identifying potential function of this microbe in the honey bee superorganism.© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.