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Mycobacteria secretes a waxy coating which makes the disease, Tuberculosis difficult to treat using antibiotics. The cellular envelope of Mycobacteria is thick, waxy and hydrophobic in nature thus, making it antibiotic resistant. The presence of mycolic acid (MA) in abundance within the mycobacterial cell envelope mainly provides the hydrophobic barrier to antibiotic entry.
What is Mycobacteria?
Mycobacterium tuberculosis is a non-motile, aerobic, waxy, lipid-rich bacillus with a high concentration of mycolic acid in its outer wall (a type of fatty acid).
What is the cell wall structure of Mycobacteria?
Mycobacteria is partially gram negative and partially gram positive in nature. The cellular envelope of mycobacteria is composed of dual membrane structure. The structure comprises of a mycobacterial outer membrane (MOM) with inner layer of mycolic acids along with outer leaflet composed of free lipids. The mycolic acid layer is covalently bonded to the polysaccharide cell wall, but the free lipids are not bound and can be removed from the envelope, a characteristic not present in Gram-negative bacteria.
What is mycolic acid?
Mycolic acids are abundantly present in the mycobacterial cell envelope contributing to 30% of the dry weight. Mycolic acids not only provide the hydrophobic barrier but also contributes to the pathogenicity of Mycobacteria. MA is composed of long-chain α-alkyl-β-hydroxy fatty acids.
What is the role of mycolic acid in antibiotic resistance?
The MA profile is specific to specific species of Mycobacteria. The MA chains are densely arranged into parallel arrays that are parallel to the cell envelope's surface, and these arrays may be stabilized by hydrogen bonds formed between the -OH groups. The cis-double bonds and cyclopropane rings, which cause kinks in the long chains, influence how the MAs fold into energetically advantageous conformations within these arrays. Stabilizing hydrophilic contacts are also formed through the oxygen functions. As a result, the keto-MAs might adopt a conformation known as the "W-form," in which four chains are arranged parallel to one another. Although the 'W' shape can also be formed by the methoxy-MAs and '-MAs, they are more malleable at higher temperatures, especially the '-MAs, which take on more open forms. The MA monolayer gains the necessary rigidity from this tight packing, creating a hydrophobic permeability barrier that may be controlled by the MAs adopting different conformations depending on their structure and the surrounding temperature.
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