Eberly College of Arts and Sciences
Microbiology, Immunology, and Cell Biology
Reductive genome evolution has purged many metabolic pathways from obligate intracellular Rickettsia (Alphaproteobacteria; Rickettsiaceae). While some aspects of host-dependent rickettsial metabolism have been characterized, the array of host-acquired metabolites and their cognate transporters remains unknown. This dearth of information has thwarted efforts to obtain an axenic Rickettsia culture, a major impediment to conventional genetic approaches. Using phylogenomics and computational pathway analysis, we reconstructed the Rickettsia metabolic and transport network, identifying 51 host-acquired metabolites (only 21 previously characterized) needed to compensate for degraded biosynthesis pathways. In the absence of glycolysis and the pentose phosphate pathway, cell envelope glycocon- jugates are synthesized from three imported host sugars, with a range of additional host-acquired metabolites fueling the tricarboxylic acid cycle. Fatty acid and glycero- phospholipid pathways also initiate from host precursors, and import of both iso- prenes and terpenoids is required for the synthesis of ubiquinone and the lipid car- rier of lipid I and O-antigen. Unlike metabolite-provisioning bacterial symbionts of arthropods, rickettsiae cannot synthesize B vitamins or most other cofactors, accen- tuating their parasitic nature. Six biosynthesis pathways contain holes (missing en- zymes); similar patterns in taxonomically diverse bacteria suggest alternative en- zymes that await discovery. A paucity of characterized and predicted transporters emphasizes the knowledge gap concerning how rickettsiae import host metabolites, some of which are large and not known to be transported by bacteria. Collectively, our reconstructed metabolic network offers clues to how rickettsiae hijack host met- abolic pathways. This blueprint for growth determinants is an important step toward the design of axenic media to rescue rickettsiae from the eukaryotic cell.
Digital Commons Citation
Driscoll, Timothy P.; Verhoeve, Victoria I.; Guillotte, Mark L.; Lehman, Stephanie S.; Rennoll, Sherri A.; Beier-Sexton, Magda; Rahman, M Sayeedur; Azad, Abdu F.; and Gillespie, Joseph J., "Wholly Rickettsia! Reconstructed Metabolic Profile of the Quintessential Bacterial Parasite of Eukaryotic Cells" (2017). Faculty & Staff Scholarship. 1519.
Driscoll, T. P., Verhoeve, V. I., Guillotte, M. L., Lehman, S. S., Rennoll, S. A., Beier-Sexton, M., … Gillespie, J. J. (2017). Wholly Rickettsia ! Reconstructed Metabolic Profile of the Quintessential Bacterial Parasite of Eukaryotic Cells. mBio, 8(5). https://doi.org/10.1128/mbio.00859-17