Mycobacteria and the great wall

The mycobacterial cell wall is unique, thick waxy, and hydrophobic, ensuring its survival inside human macrophages by resisting oxidative damages. The waxy, highly impermeable nature of the wall provides the required defense mechanism against antibiotic agents and the host organisms. A key component of the cell wall is mycolic acids. Mycolic acid accounts for up to 60% of the organisms' dry weight, which means that most percentage of mycobacteria is a cell wall. A thorough understanding of the influence of polarity on drug penetration into a highly impermeable mycobacterial cell wall will improve permeability.

The permeation ability of a lipophilic molecule is inversely related to the cell wall's fluidity, which decreases as the length of fatty acids in the mycolic acids layer increases. The permeability barrier presented by this cell envelope is also thought to be why many common antibiotics are ineffective against mycobacteria. Lipophilic drugs, such as fluoroquinolones or rifamycins, pass more quickly through the lipid-rich cell wall and thus are more active.

Depending on the library screens towards compounds with a particular physicochemical parameter could be detrimental and decrease the diversity in finding new anti-TB drugs.