# Modulation of Host Lipid Pathways by Pathogenic Intracellular Bacteria
## 2 Intracellular Bacteria That Replicate Inside a Vacuole during Infection
### Host Lipids Provide Structural Integrity to Pathogen-Associated Membranes  
Bacterial membranes are limited in their composition of lipid species when compared to their eukaryotic counterparts. The predominant lipids present in standard Gram-negative and Gram-positive bacterial membranes are cardiolipin, phosphatidylglycerol (PG), phosphatidylethanolamine (PE),phosphatidic acid (PA), and phosphatidylserine (PS), with machinery lacking for biosynthesis of cholesterol and, in some intracellular bacteria, phosphatidylcholine (PC). In general, bacterial membrane lipids are unsaturated and can exhibit distinct branching patterns among the various bacteria [24; 25]. Many vacuolar intracellular bacteria recruit and incorporate specific host lipids as structural components for both the host-derived PCVs and bacterial membrane. Although, intracellular bacteria do not encode the enzymes necessary for production of cholesterol and other lipids commonly found within eukaryotic cells, they have adapted mechanisms for modification of sequestered host lipids for incorporation into structural membranes during infection. _Chlamydia_ spp. are vacuolar pathogens that typically target epithelial cells in areas of species-specific tropism and can actively replicate in vacuoles within recruited macrophages during infection [26]. A characteristic of the _Chlamydia_-PCV is that the membrane contains Golgi apparatus-derived membrane markers indicative of a non-acidic, nutrient-rich vacuole unlikely to interact with the lysosome during late stages of the endocytic pathway [27; 28]. Association of the PCV with the host Golgi apparatus, which acts as a nutrient-rich recycling and trafficking organelle, also provides nutrients to the bacteria. During human and mouse fibroblast infection, the _Chlamydia_-containing vacuole contains cholesterol-rich microdomains that comprise an abundance of PCV membrane-associated bacterial proteins (Figure 1). These bacterial PCV proteins are important for interacting with the host proteins, such as Src-family kinases, to modulate vacuole trafficking via the host microtubule network. This trafficking is required to facilitate the PCV and Golgi-derived endosome fusion for nutrient sharing and genetic exchange required for the development of disease [29; 30; 31]. In addition to the incorporation of host cholesterol into the PCV, _Chlamydia_ spp., such as _C. trachomatis_ and _C. pneumoniae_, also actively recruit host cholesterol and free fatty acids through initiation of exogenous lipoprotein recruitment and de novo lipid synthesis for fatty acid overaccumulation within host cells [27; 32] (Figure 1). Interestingly, during _C. trachomatis_ infection of Hep-2 epithelial cells and mouse and human fibroblasts, host compartments, such as lipid droplets (LDs) and host peroxisomes, along with free fatty acids, colocalize at the PCV [33; 34]. The association of these host cellular components at the PCV allows for efficient peroxisome-driven lipolysis of associated fatty acids, specifically PC and lysophosphatidylcholine (lyso-PC), that are unable to be made by _C. trachomatis_. It is important to note that although peroxisome-driven lipolysis is a known source of lipids for the bacteria, lipid droplet-associated lipases are also likely involved in providing the required lipids for _C. pneumoniae_ growth [33]. Thus, these events allow _C. trachomatis_ to scavenge and modify the catabolized lipids for incorporation in the bacterial membrane [33; 35; 36; 37] (Figure 1). Both host and chlamdial proteins play crucial roles in the sequestering and modification of host PC for incorporation into the bacterial membrane. Specifically, the proteins involved in PC modification are the human proteins, human acyl-CoA:lyso-PC acyltransferase 1, CLA1 lipid transporter, and human acyl-CoA carrier 6, along with the pathogen protein, chlamdial lyso-PC acyltransferase. The combination of these proteins ultimately re-acetylates host PC for bacterial use.