Role of lipids in Coxiella burnetii infection.

Lipids are essential components of both eukaryotic and prokaryotic cells, serving diverse functions including energy metabolism and membrane structure. Intracellular vacuolar pathogens such as Coxiella burnetii require lipids for both normal bacterial functions as well as formation of the acidic, phagolysosomal-like parasitophorous vacuole (PV) surrounding the bacteria. As an intracellular pathogen, C. burnetii can acquire lipid through both de novo bacterial synthesis and subversion of host cell pools. The C. burnetii genome encodes enzymes required for de novo synthesis of fatty acids and phospholipids. The high percentage of branched fatty acids suggests C. burnetii modifies these molecules to generate a bacterial cell envelope that can resist the harsh environment of the PV, such as the acidic pH. In addition to fatty acids and their derivatives, C. burnetii requires isoprenoids, particularly sterols as the PV membrane is cholesterol-rich. With the exception of two eukaryote-like sterol reductases, C. burnetii does not have the capability to generate cholesterol, suggesting sterols are actively diverted from the host cell. While C. burnetii utilizes host cell lipids for membrane biogenesis and possibly energy, bacterial manipulation of host cell lipid signaling pathways may support establishment of the intracellular niche. For example, effectors secreted by the C. burnetii Type IV secretion system may either directly or indirectly modify host cell lipids. Further understanding of the lipid biosynthetic capabilities of C. burnetii, along with C. burnetii's manipulation of host cell lipids, will provide insight into the host-pathogen relationship.