What is mycolic acid synthesis?
Biosynthesis of mycolic acid precursors requires two types of fatty acid synthases (FASs), the eukaryotic-like multifunctional enzyme FAS I and the acyl carrier protein (ACP)-dependent FAS II systems, which consists of a series of discrete mono-functional proteins, each catalyzing one reaction in the pathway.
What is the purpose of mycolic acid?
tuberculosis cell walls contain fatty molecules known as mycolic acids, which make the bacteria less susceptible to antibiotics. These molecules also help the bacteria to subvert and then hide from the immune system.
What does mycolic acid inhibit?
The drugs shown to inhibit mycolic acid biosynthesis are isoniazid, ethionamide, isoxyl, thiolactomycin, and triclosan. In addition, pyrazinamide was shown to inhibit fatty acid synthase type I which, in turn, provides precursors for fatty acid elongation to long-chain mycolic acids by fatty acid synthase II.
What blocks the synthesis of mycolic acid in Mycobacterium?
ISO has been shown to inhibit the biosynthesis of both mycolic acids and fatty acids in M.
Is mycolic acid a glycolipid?
The unique composition of the cell wall composed of mycolic acid, glycolipids such as diacyltrehaloses, polyacyltrehalose, lipomannan, lipoarabinomannan (LAM), mannose-capped-LAM, sulfolipids, and trehalose-6,6′-dimycolate, all have been implicated in providing the pathogen an advantage in the host.
What is mycolic acid and what properties does it confer on mycobacteria?
Mycolic acids are major and specific lipid components of the mycobacterial cell envelope and are essential for the survival of members of the genus Mycobacterium that contains the causative agents of both tuberculosis and leprosy.
Where are mycolic acids found in mycobacteria?
cell walls
Mycolic acids are unique long chain fatty acids found in the lipid‐rich cell walls of mycobacteria including the tubercle bacillus M ycobacterium tuberculosis. Essential for viability and virulence, enzymes involved in the biosynthesis of mycolic acids represent novel targets for drug development.
Is mycolic acid a virulence factor?
Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern. Eur J Immunol.
What is the significance of mycolic acids in the cell walls of acid-fast organisms?
Functions of the Acid-Fast Cell Wall Components Layer 3: The mycolic acids and other glycolipids also impede the entry of chemicals causing the organisms to grow slowly and be more resistant to chemical agents and lysosomal components of phagocytes than most bacteria (Figure 2.3C. 2).
Where is mycolic acid found?
Mycolic acids are unique long chain fatty acids found in the lipid‐rich cell walls of mycobacteria including the tubercle bacillus M ycobacterium tuberculosis.
Why do we use acid-fast staining for Mycobacterium?
This stain is used to identify Mycobacterium tuberculosis, the causative agent of tuberculosis. Acid-fast organisms have a lipoid capsule that has a high molecular weight and is waxy at room temperature. This makes the organism impenetrable by aqueous-based staining solutions.
Is mycolic acid hydrophobic?
In rhodococci, mycolic acids have between 54 and 60 carbon atoms and may represent up to 40% of the cell wall composition [7], [8]. As a result, rhodococci cells are hydrophobic, allowing adhesion at the oil/water interphase.
What is the pathophysiology of lipid A biosynthesis?
Lipid A biosynthesis pathway. E. coli lipid A biosynthesis proceeds through nine enzyme-catalyzed steps, which are sometimes referred to as the Raetz pathway [ 2 ], [ 7] ( Fig 2 ). All of these enzymes are constitutively expressed [ 5].
How are enzymes involved in lipid A biosynthesis in Escherichia coli?
We developed a quantitative model of the nine enzyme-catalyzed steps of Escherichia coli lipid A biosynthesis, drawing parameters from the experimental literature. This model accounts for biosynthesis regulation, which occurs through regulated degradation of the LpxC and WaaA (also called KdtA) enzymes.
Does lipid A biosynthesis control pathway flux?
These results show that control of pathway flux is typically localized to relatively few enzymes, but ones which depend on the substrate concentrations. Next, we investigated the sensitivity of lipid A biosynthesis on enzyme counts for the case of large perturbations, assuming saturating substrate concentrations.
How is lipid A synthesis regulated?
Lipid A synthesis is regulated, at least in part, through controlled degradation of LpxC [ 47 ], [ 48 ], [ 49] and WaaA [ 50], both performed by FtsH (EC 3.4.24.—). FtsH is an integral membrane AAA-type metalloprotease that degrades a wide variety of proteins.