Mycobacterial outer membranes: in search of proteins

The cell wall is a major virulence factor of Mycobacterium tuberculosis and contributes to its intrinsic drug resistance. Recently, cryo-electron microscopy showed that mycobacterial cell wall lipids form an unusual outer membrane. Identification of the components of the uptake and secretion machinery across this membrane will be crucial for understanding the physiology and pathogenicity of M. tuberculosis and for the development of better anti-tuberculosis drugs. Although the genome of M. tuberculosis appears to encode over 100 putative outer membrane proteins, only a few have been identified and characterized. Here, we summarize the current knowledge on the structure of the mycobacterial outer membrane and its known proteins. Through comparison to transport processes in Gram-negative bacteria, we highlight several hypothetical outer membrane proteins of M. tuberculosis that await discovery.