Wholly Rickettsia! Reconstructed Metabolic Profile of the Quintessential Bacterial Parasite of Eukaryotic Cells.

摘要: 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 host-acquired metabolites and their cognate transporters remains unknown. This dearth information thwarted efforts to obtain an axenic culture, a major impediment conventional genetic approaches. Using phylogenomics computational pathway analysis, we reconstructed transport network, identifying 51 (only 21 previously characterized) needed compensate for degraded biosynthesis pathways. In absence glycolysis pentose phosphate pathway, cell envelope glycoconjugates are synthesized three imported host sugars, with range additional fueling tricarboxylic acid cycle. Fatty glycerophospholipid also initiate precursors, import both isoprenes terpenoids is required synthesis ubiquinone lipid carrier I O-antigen. Unlike metabolite-provisioning bacterial symbionts arthropods, rickettsiae cannot synthesize B vitamins or most other cofactors, accentuating parasitic nature. Six contain holes (missing enzymes); similar patterns in taxonomically diverse bacteria suggest alternative enzymes that await discovery. A paucity characterized predicted emphasizes knowledge gap concerning how metabolites, which large not known be transported by bacteria. Collectively, our network offers clues hijack blueprint growth determinants important step toward design media rescue eukaryotic cell.IMPORTANCE hallmark tradeoff genes ability acquire metabolites. For species Rickettsia, arthropod-borne parasites potential cause serious human disease, pilfered critical dissociating cells facilitate manipulation. this study, identified patchwork Remarkably, any bacteria, overall, few were identified. Several missing enzymes, yet unrelated indicate convergence possible novel awaiting characterization. Our work illuminates nature counterbalance numerous disintegrated arisen through within cell. reveals what medium might entail.