Characterizing the early stages of a novel host shift using host fitness and metabolomics

The factors that contribute to successful colonization of a novel host species by a pathogen remain unclear. One likely factor determining host shift success is the early interaction between host and pathogen at the very moment of the host shift event. How does a novel host respond to a pathogen insult immediately following infection? To answer this question, the Drosophila model was used along with the highly pathogenic Drosophila C virus, host fitness assays and metabolomic analysis to measure the host’s response to a novel pathogenic infection. As Wolbachia can interfere with RNA virus infection success, a new method was developed to reliably and quickly eliminate Wolbachia from the flies. Once the flied were confirmed to be Wolbachia-free, they were injected with DCV. Females of the native host (D. melanogaster) and the novel host (D. mauritiana) were injected with DCV or Schneider’s media, subjected to fitness tests, frozen in liquid nitrogen and their metabolomes were analyzed. The novel host had equal or increased fitness (fecundity, hatchability, pupation, number of pupae, and number of adults), but significantly higher mortality. Metabolomic analysis revealed that many metabolites from a variety of metabolic pathways were significantly different. A wide range of stress-related metabolites were upregulated in the native host, but not in the novel host. These results support the hypothesis that the initial physiological interaction between a pathogen and its novel host is critical for the survival of the host or the success of the pathogen