ECH is the rate-limiting enzyme in beta oxidation and may be downregulated in order to reduce energy availability, as a means to reduce pathogen replication within 
cells. Shutting down beta oxidation would tend to reduce the availability of ATP and acetyl CoA, as diagrammed in figure S3. The two carbon acetyl compound carried by AcCoA is a central intermediate in energy metabolism that is derived from the breakdown of glucose, fatty acids, or ketogenic amino acids. AcCoA serves as the entry point into the Krebs cycle, which is a key component of aerobic energy generation, including the production of NADH and FADH2, which carry electrons to the respiratory electron transport chain. The response of mouse liver cells to LPS stimulation was recently reported to induce steatosis, the excessive retention of lipids in the liver, which reduces the lipids available for energy generation. While the overall alterations to the proteome suggest an innate immune response is being activated by C. burnetii infection, there are also points of interest related to C. burnetii biology. The elevation of S100A8/9 as well as vimentin suggests the onset of macrophage differentiation as pointed out above. The elevation of apparently intact vimentin suggests that caspases are not highly active in the infected cells, consistent with observations that C. burnetii can inhibit caspase activation. The changes in the two Rab7 isoforms in our experiments, as well as observations that Rab7 is a lipid raft associated protein, warrants further scrutiny. Rab7 would be predicted to be critical to C. burnetii’s metabolic and replicative activities as detailed above. Disruption of cellular lipid raft remodeling by disruption of cholesterol synthesis with statins is expected to have a synergistic effect with antibiotic and/ or immune adjuvant Amikacin hydrate treatment protocols. Therefore, altering the composition of lipid rafts might be an attractive mechanism for C. burnetii to modulate Rab7 and vATPase localization. The recent work by Howe et al., demonstrated that phase I and phase II C. burnetii induced phenotypically indistinguishable responses from both primary and cultured monocytes at least with regards to the replicative vacuole. These findings support the use of phase II C. burnetii in cultured monocytes as a model system for studying C. burnetii-host cell interactions. It is also of note that Vero cells, a Green monkey kidney epithelial cell, commonly used in C. burnetii investigations, tends to give similar results to those obtained in monocytic cells. This suggests that C. burnetii infections have similar effects on a variety of different cell types and suggests further that the system used in our investigation can be extended to pathogenic conditions in primary cells. The observation of C. burnetii’s effects on NADPH oxidase assembly, coupled with the observation that lipid rafts regulate the activation state of NADPH oxidase in renal cells, further 4-(Benzyloxy)phenol supports the hypothesis that C. burnetii infections are able to regulate the lipid raft composition of the host cell. The finding that cholesterol depletion increased NADPH oxidase activity in renal cells, supports the hypothesis that inhibiting cellular cholesterol production in combination with other treatments could improve therapeutic approaches to Q fever infection. The changes in protein expression described above, as well as the proposed functions of the regulated proteins in this system would be predicted to be similar between phase I C. burnetii and phase II, as well as between Monomac I cells and primary monocytes.