# Modulation of Host Lipid Pathways by Pathogenic Intracellular Bacteria
## 1 Introduction  
Lipids are broadly described as hydrophobic or amphipatic molecules that are involved in various biological functions including mediating immune signaling, regulating vesicle trafficking, providing energy storage and production, and structural membrane composition [1; 2; 3; 4; 5; 6; 7; 8; 9; 10]. Lipids are a large, diverse group of molecules that provide various specific functions required by the host cell to maintain homeostasis. These lipids can be divided into various classes that are highly organized and provide very specialized functions [5]. Furthermore, because of the essentiality and multifunctional property of host lipids for cell maintenance, intracellular pathogens have adapted mechanisms to employ a number of these lipids throughout infection for both host cell regulation, and pathogen replication and sustainability [11]. Intracellular pathogens modify host lipid composition by regulating host cell uptake of exogenous lipids from the environment and modulating the expression of enzymes involved in the host de novo lipid biosynthetic pathways [12; 13; 14; 15; 16]. This alteration in host lipid composition can be beneficial to the pathogen by providing a number of different functions including: (i) Employing storage and/or free lipids for energy production. Fatty acids within host lipid storage compartments, known as lipid droplets (LDs), and free fatty acids can be catabolized by various methods, such as lipolysis, lipophagy, and selective breakdown via phospholipases. These processes differ in that lipolysis releaseslipids through hydrolysis, lipophagy utilizes host autophagy machinery to breakdown lipids within lipid droplets, and phospholipes selectively catabolize specific species of lipids some of which are associated with LDs. The lipids released can then be used in the \(\beta\)-fatty acid oxidation (FAO) pathway, which enzymatically breaks down fatty acids to acetyl-CoA for use in oxidative phosphorylation (OXPHOS) for energy production [17]. Pathogens are also able to release and sequester metabolites within these catabolic pathways by use of bacterial phospholipes for self-generation of energy. The regulation of host lipid metabolism to promote shifts in energy production pathways has also been implemented in modulating host cell persistence, pathogen sustainability, and anti-inflammatory mechanisms. (ii) Pathogen membrane production. Some intracellular pathogens have been shown to have unique lipids within their membrane structures that are unlike common bacterial lipids and that are unable to be made by the pathogen machinery encoded in the genome. Thus, is it likely that the lipids are acquired from the host and are incorporated into the pathogen membrane. (iii) Invasion of host signaling pathways and the host immune system. Lipid organization within host membranes play an important role in the regulation of signaling pathways by creating \"hot spots,\" known as lipid rafts, for enabling the association of receptors with external and internal stimuli. These functional, highly organized membrane regions are utilized by various intracellular bacterial pathogens for entry into the host cell [18]. There are also fatty acid molecules released from LDs, such as arachidonic acids, that are precursors of host immune modulators, such as prostaglandandins and leukotrienes, and have a key role in the presentation of disease during pathogen infection [19; 20; 21]. Human pathogenic intracellular bacteria have developed mechanisms that initiate the employment of host lipids to cause disease during mammalian infection. Among the functions that require host lipids are bacterial entry into the host cell, formation of an intracellular compartment, metabolic requirements for bacterial survival and replication, and disease initiation and progression. However, because intracellular bacterial pathogens differ in the mechanisms used to colonize cells, it is likely that host lipid manipulation during infection varies between different bacterial species [22].