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 A
2 [
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.
---
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.
