Mycobacterium tuberculosis mycolic acid and cell wall biosynthesis pathway (Mtb cell wall biosynthesis pathway)

The Mycobacterium tuberculosis mycolic acid and cell wall biosynthesis pathway is a complex metabolic network essential for the structural integrity and virulence of the TB-causing bacterium. The cell wall is characterized by a unique 'mycomembrane' composed of long-chain fatty acids called mycolic acids, which are covalently linked to an arabinogalactan-peptidoglycan complex. This dense, waxy barrier provides exceptional protection against environmental stress, host immune responses, and many conventional antibiotics. Key components of this pathway include the Fatty Acid Synthase I and II (FAS-I and FAS-II) systems, which work in tandem to produce the long carbon chains required for mycolic acid assembly. Because many of these enzymes have no human homologs, the pathway is a primary target for frontline anti-tuberculosis drugs like isoniazid and ethambutol. Disruption of this pathway leads to loss of acid-fastness, cell wall instability, and ultimately bacterial cell death.

Other names

Mycolic acid biosynthesisMtb cell wall synthesisFAS-II systemArabinogalactan biosynthesisPeptidoglycan biosynthesis

Inhibition of specific enzymes within the pathway, such as InhA (enoyl-ACP reductase) by isoniazid and ethionamide, EmbB (arabinosyltransferase) by ethambutol, and Ddn (deazaflavin-dependent nitroreductase) mediated inhibition of mycolic acid synthesis by delamanid and pretomanid.