TB bakteerin metaboliasta ja lipidikalvosta

https://www.intechopen.com/books/lipid-metabolism/metabolism-of-plasma-membrane-lipids-in-mycobacteria-and-corynebacteria

Tubibakteeri on  esimerkillinen  yhdessä asiassa: Sen tekemä suojavalli on todella  mahtava.
täytyy etsiä siinä olevia heikkoja kohtia. ydhen havaitsin juuri. TBC bakteeri vaikka se osaa tehdä yhtä ja toista, se ei osaa tehdä kolesterolia, vaan tarvitsee  isäntäkehosta sitä. Kolesteroli on sille  mm energia-aine, mitä se taas ei ole ihmisessä, vaan ihminen erittää kolesterolin  lopulta.

Studies on mycobacteria and corynebacteria provide a unique opportunity to illustrate the complexity and diversity of lipid metabolic pathways in bacteria. They have a significantly higher lipid content than other bacteria with cell wall lipids comprising ~40% of the dry cell mass. M. tuberculosis produces a diversity of lipids unparalleled in bacteria, from simple fatty acids to highly complex long chain structures such as mycolic acids. It has devoted a significant proportion of its coding capacity to lipid metabolism and produces about 250 enzymes dedicated to fatty acid metabolism, which is around five times the number produced by Escherichia coli [5]. Lipid biosynthesis places a significant metabolic burden on the organism but is ultimately advantageous, allowing M. tuberculosis to survive and replicate in the inhospitable environment of host macrophages. While capable of de novo synthesis, these bacteria also scavenge and degrade host cell membrane lipids to acetyl-CoA, via broad families of β-oxidation and other catabolic enzymes, for incorporation into their own metabolic pathways and to fuel cellular processes.

(Kardiolipiinistä (CL): ihmisellä on kardiolipiiniä mitokondrioitten kalvossa. mitokondriat ovat taas  ihmisen energialaitoksia)

CL is widely found in both prokaryotes and eukaryotes. It forms aggregates within the membrane bilayer. Nonyl acridine orange (NAO) is a fluorescent dye which is proposed to bind the hydrophobic surface created by the CL cluster [14], allowing microscopic visualization of CL domains. Indeed, using NAO, CLs were found to be enriched in septa and poles of actively dividing M. tuberculosis and M. smegmatis cells [15, 16]. CL has a non-bilayer structure [17, 18], and carries a small partially immobilized head group that is more exposed to the aqueous environment than those of other glycerophospholipids [19]. Although the physiological function of CL is unclear, its physical properties may indicate that it provides a platform for membrane-protein interactions. Indeed, some mycobacterial enzymes require CL for activity [20-22], although the molecular basis for these observations has not been clarified. Recent fractionation studies in C. glutamicum revealed that CL (as well as other phospholipids) is enriched in the plasma membrane [23, 24]. However, a large proportion of CL is also found to be associated with the outer membrane [24], suggesting that some of these phospholipids are exported to the outer membrane in corynebacteria. Similarly, CL is released from M. bovis bacillus Calmette-Guerin residing in host phagosomes, and converted to lyso-CL by a host phospholipase A₂ [25]. It has been suggested that lyso-CL may influence host immune responses during infection.

 (Tässä tulee mieleen että  TB bakteeri saattaa  soluja tuhotessaan  ryöstää näitä alunperin mitokondriaalisia   kardiolipiinejä soluilta ja kuljettaa omaan plasmakalvoonsa ja silloin sen energiatalous paranee ja  TB pääsee ns.  "niskan päälle".

TB bakteeri  akkumuloi kolesterolia isäntäsoluista.

Cholesterol has recently been suggested to be an alternative form of lipid storage in mycobacteria. Neither mycobacteria nor corynebacteria have the capacity to synthesize cholesterol. However, cholesterol is taken up by M. tuberculosis cells residing in the host, and components of the mce4 operon have been shown to be involved in cholesterol import [55]. Cholesterol catabolism is critical in the chronic phase of animal infection, and a fully functional catabolic pathway is encoded by the M. tuberculosis genome [56]. Furthermore, cholesterol appears to accumulate in the mycobacterial cell envelope, and this might represent a potential form of lipid storage for M. tuberculosis during animal infection [57, 58]. Although the authors of this study suggested that cholesterol accumulates in the outer membrane, it remains possible that the plasma membrane is the true site of accumulation. Therefore, in addition to acting as a lipid storage molecule, cholesterol may play roles in plasma membrane structure and function, and these possibilities await further exploration.
Catabolism of cholesterol, amino acids and odd-chain-length/methyl branched fatty acids produces propionyl-coenzyme A (CoA). Propionate accumulation has been shown to be toxic in various organisms [59-61], and M. tuberculosis has multiple pathways to metabolize propionyl-CoA [62]. Metabolized propionyl-CoA is in part incorporated into TAG [63], and it has been suggested that TAG functions as a sink for reducing equivalents in addition to being a source of carbon and energy.

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3.1. Fatty acids

M. tuberculosis devotes a large proportion of its coding capacity to genes involved in fatty acid metabolism [5], highlighting the importance of lipids to the organism. Fatty acid metabolism is essential for intracellular survival of the pathogen since it forms the precursors of key membrane components such as plasma membrane phospholipids and outer membrane glycolipids. In particular, mycolic acids, which are very long chain α-alkyl β-hydroxy fatty acids, form the hydrophobic, protective mycomembrane described earlier.