Résumé
The mycobacterial cell wall is essential for Mycobacterium tuberculosis growth and survival. It is lipid‐rich and highly impermeable and thereby provides protection from many antibiotics, and also allows the pathogen to proliferate within macrophages and to persist for extended periods of time in the infected host (1). Mycolic acids, which are long‐chain α‐alkyl β‐hydroxy fatty acids, constitute up to 60% of the cell wall and are principally responsible for the low permeability of the waxy cell envelope (2). They are found primarily as esters of the nonreducing arabinan terminus of arabinogalactan (AG) but are also present as extractable “free” lipids within the cell wall, mainly associated with trehalose to form trehalose dimycolate (TDM), also known as cord factor (3). Recent studies have also demonstrated the presence of free mycolates associated with M. tuberculosis biofilms (4). The crucial importance of the cell envelope integrity for the viability of M. tuberculosis has raised interest in understanding the enzymatic pathway for mycolic acid biosynthesis (5). Our knowledge of the biosynthesis of mycolic acid is important for finding new therapeutic targets to combat tuberculosis as well as for unraveling the mode of action of several existing antitubercular drugs (6 – 8). Indeed, the inhibition of mycolic acid biosynthesis is the primary effect of the frontline drug isoniazid (INH) (9). This unique metabolic pathway represents an important and attractive reservoir of targets for future chemotherapy, whose development is particularly urgent in the context of multidrug‐resistant (MDR) tuberculosis and the nearly untreatable (10) extensively drug‐resistant (XDR) strains of M. tuberculosis.