biostudies-literatureAhyong VHHS | National Institutes of HealthNCRR NIH HHSNIAID NIH HHSNCI NIH HHSe00536-19https://www.ebi.ac.uk/biostudies/studies/S-EPMC6854040biostudies-literatureUnknown4(6)Gram-negative bacteria in the order <i>Rickettsiales</i> have an obligate intracellular growth requirement, and some species cause human diseases such as typhus and spotted fever. The bacteria have evolved a dependence on essential nutrients and metabolites from the host cell as a consequence of extensive genome reduction. However, it remains largely unknown which nutrients they acquire and whether their metabolic dependency can be exploited therapeutically. Here, we describe a genetic rewiring of bacterial isoprenoid biosynthetic pathways in the <i>Rickettsiales</i> that has resulted from reductive genome evolution. Furthermore, we investigated whether the spotted fever group <i>Rickettsia</i> species <i>Rickettsia parkeri</i> scavenges isoprenoid precursors directly from the host. Using mSphereA Metabolic Dependency for Host Isoprenoids in the Obligate Intracellular Pathogen Rickettsia parkeri Underlies a Sensitivity to the Statin Class of Host-Targeted Therapeutics.PMC6854040R01 CA172667R21 AI109270S10 RR027696F32 AI133912R01 AI109044Ahyong VBurke TPNomura DKBerdan CAWelch MDfalseA Metabolic Dependency for Host Isoprenoids in the Obligate Intracellular Pathogen Rickettsia parkeri Underlies a Sensitivity to the Statin Class of Host-Targeted Therapeutics.Gram-negative bacteria in the order <i>Rickettsiales</i> have an obligate intracellular growth requirement, and some species cause human diseases such as typhus and spotted fever. The bacteria have evolved a dependence on essential nutrients and metabolites from the host cell as a consequence of extensive genome reduction. However, it remains largely unknown which nutrients they acquire and whether their metabolic dependency can be exploited therapeutically. Here, we describe a genetic rewiring of bacterial isoprenoid biosynthetic pathways in the <i>Rickettsiales</i> that has resulted from reductive genome evolution. Furthermore, we investigated whether the spotted fever group <i>Rickettsia</i> species <i>Rickettsia parkeri</i> scavenges isoprenoid precursors directly from the host. Using 2019-01-01T00:00:00Z2019 Nov2026-06-17T06:54:58.853Z2020-05-22T10:49:07ZS-EPMC68540403172299110.1128/mSphere.00536-19