Science 2003,300(5624):1404–1409.PubMedCrossRef Authors’ contributions CA, JG, CM, MC performed the research. CA, OH, MC, OB analysed the data. DB, JD, UD, ED participed to the coordination of the study. OB wrote the paper. All authors see more read and approved the final manuscript.”
“Background The cell envelope of members of the selleckchem Mycobacterium genus contains a unique array of structurally-complex free lipids thought to be non-covalently bound to the mycolic acid layer of the cell wall [1–3]. These free lipids are believed to form a membrane outer leaflet that partners with a mycolic acid-based membrane inner leaflet to form an

asymmetric lipid bilayer-like structure. This lipid bilayer constitutes the distinctive outer membrane of the mycobacterial Proteases inhibitor cell envelope. The documented role of some of these free lipids as mycobacterial virulence effectors highlights the enzymes involved in their production as potential target candidates for exploring the development of novel drugs that could assist conventional antimicrobial therapy in the control of mycobacterial infections. Notably, the first inhibitor of the biosynthesis of a group of these free lipids (i.e., phenolic glycolipids [3]) has been recently reported [4]. The inhibitor works in a manner analogous to that of the first reported inhibitor of siderophore (iron chelator) biosynthesis [5, 6], and it blocks the production of phenolic glycolipids in Mycobacterium tuberculosis

and other mycobacterial before pathogens [4]. Glycopeptidolipids (GPLs) are among the major free glycolipid components of the outer membrane of several Mycobacterium species [7, 8] (Figure 1). The GPL-producing

species include saprophytic mycobacteria, such as Mycobacterium smegmatis (Ms), and many clinically-relevant nontuberculous mycobacteria. The members of the Mycobacterium avium-Mycobacterium intracellulare complex (MAC) are among the GPL producers of clinical significance. MAC infections cause pulmonary and extrapulmonary diseases in both immunocompromised and immunocompetent individuals [9, 10]. Importantly, GPLs have been implicated in many aspects of mycobacterial biology, including host-pathogen interaction [11–17], sliding motility [18, 19], and biofilm formation [18, 20]. An altered expression profile of GPLs has been observed in drug-resistant clinical isolates of MAC [21], a finding that raises the possibility that GPL production might have an impact on drug susceptibility as well. Thus, elucidation of the GPL biosynthetic pathway is important not only because it will expand our understanding of cell wall biosynthesis in mycobacteria, but it may also illuminate potential routes to alternative therapeutic strategies against infections by MAC and other opportunistic mycobacterial human pathogens. Figure 1 Representative structures of glycopeptidolipids. The depicted GPLs correspond to those found in Mycobacterium smegmatis.