# Modulation of Host Lipid Pathways by Pathogenic Intracellular Bacteria
## 2 Intracellular Bacteria That Replicate Inside a Vacuole during Infection
### Host Lipid-Droplet Modulation
The regulation of ATGL and FABP4 indicate a release of free fatty acids and cholesterol from host LDs for _C. burnetii_ nutrient acquisition and membrane production as described previously [82]. _C. burnetii_ also encodes a bacterial phospholipase A enzyme that is involved in accumulating free fatty acids, possibly for membrane and energy production or immune regulation during infection [86]. Similar to _C. trachomatis_, _C. burnetii_ infection also utilizes prostaglandandins derived from host LD intermediates to promote intracellular growth and disease presentation [87; 88; 89] (Figure 1). Interestingly, the inhibition of acyl-CoA anabolism and de novo lipid synthesis involved in production of host LDs enhances _C. burnetii_ growth during macrophage infection. Conversely, pharmacological inhibition of LD catabolism is detrimental to _C. burnetii_ infection. Together,these results suggest that lipids derived from host LDs and likely exogenous-derived lipids are essential for modulation of the host immune response and nutrient acquisition during _C. buntetii_ macrophage infection [82]. Little is known about the mechanisms employed to modulate host LDs during _A. phagocytosis_ and _E. chaffensis_ infection of the respective target cells. During infection of promyelocytic cells, _A. phagocytosis_ increases expression of perilipin 1 (PLIN1), the major host protein important for regulation of LD formation and lipolysis, suggesting a possible role of host LDs as a source of cholesterol and fatty acids. However, the exact function of host LDs for _A. phagocytosis_ infection is still not yet elucidated [90; 91; 92; 93; 94]. Interestingly, _E. chaffensis_ has not been shown to have an association with host LDs or LD-related host molecules. Similar to _A. phagocytosis_, the requirement of host cholesterol for successful infection implies a possible use of host LDs for cholesterol acquisition during infection. Facultative intracellular pathogens from the genus _Mycobacterium_ provide classic examples of producing a foam cell phenotype required for persistence during alveolar macrophage and overall mammalian infection. Many bacterial and host mechanisms are employed to produce and maintain the foam cell state during mycobacterial infection with various _Mycobacterium_ spp. For example, _M. tuberculosis_ and _M. leprae_ infection increases transcription of bacterial genes involved in LD accumulation, _plin2_ (coding for perilipin 2) and acyl-CoA synthase, while _M. tuberculosis_ also modulates host transcription factors PPAR\(\alpha\) and V, similar to _C. pneumoniae_[95; 96; 97; 98; 99; 100; 101]. Unlike _C. pneumoniae_, _M. tuberculosis_'s growth during infection is increased by an upregulation in PPARY and subsequent triacylglycerol production and accumulation of host LDs. _M. tuberculosis_ growth is also downregulated when LD catabolism is increased by transcription factor EB (TFEB)-initiation and subsequent PPAR\(\alpha\) expression. Together, these data suggest an importance of LD overaccumulation during macrophage infection [96; 97]. Similar to that of _C. pneumoniae_ and _C. buntetii_, _M. leprae_ infection also increases prostaglandin production, which then stimulates other immune modulatory molecules, such as IL-10 and TGF\(\beta\) required for bacterial survival and persistence [100; 102]. Interestingly, _M. tuberculosis_ is capable of producing triacylglycerol-rich bacterial LD storages during the dormancy stage of infection [98; 99; 103; 104; 105]; however, _M. tuberculosis_ still associates with host LDs suggesting utilization of host storages for nutrient acquisition to increase efficiency and persistence during long-term mammalian infection [106]. _M. tuberculosis_ and _M. leprae_ also encode phospholipase C and other bacterial lipases used to release free fatty acids from storage lipids as carbon sources for increased infection efficiency [107; 108] (Figure 1). Similar to _C. trachomatis_, _M.