Natural Genetic Variation in the Drosophila Genetic Reference Panel Reveals Genes Associated with Susceptibility or Tolerance to Coxiella burnetii Infection
Primary author: Rosa Guzman
Faculty sponsor: Alan Goodman
Primary college/unit: College of Veterinary Medicine
The Gram-negative bacterium Coxiella burnetii (C. burnetii) is the causative agent of Query (Q) fever in humans and coxiellosis in livestock. Association between host genetic background and C. burnetii pathogenesis has been demonstrated both in humans and animals; however, specific genes associated with severity of infection remain unknown. Our lab has shown that the Drosophila melanogaster model is suitable for studying host-pathogen interactions during C. burnetii infection. In this study, we employed the Drosophila Genetics Reference Panel (DGRP), a library of 209 inbred wild-type fly lines, to identify host genetic variants that affect susceptibility or tolerance to C. burnetii infection. We infected each DGRP line, monitored survival, and calculated a hazard ratio for each line to perform a genome-wide association study (GWAS). We tested 25 GWAS candidate genes by infecting flies carrying a null mutation or RNAi knockdown of each gene and monitoring survival. Of these 25 genes, 6 validated in null mutants only, 5 in RNAi knockdown only, and 4 in both null mutants and RNAi. One gene that validated in both null mutants and RNAi knockdown flies was taranis, which is essential for regeneration and JNK signaling. The human ortholog of taranis is SERTAD1, which has been recently linked to immunity. Our results demonstrate that from genes identified and validated in our genetic screen, mechanism of action studies should be performed to determine the genes’ role in the host immune response to infection.