The mycobacterial cell envelope forms an exceptionally strong barrier rendering mycobacteria naturally impermeable to a wide variety of antimicrobial agents. An integral part of their Outer Membrane (OM) is the ‘cell wall skeleton', a giant macromolecule consisting of peptidoglycan (a structure of oligosaccharides formed from disaccharide units of N-acetylglucosamine and N-glycolylmuramic acid cross-linked by short peptides), arabinogalactan (a complex branched polysaccharide) and mycolic acids (long-chain, 2-alkyl-3-hydroxy fatty acids). Physisorbed at the cell-wall skeleton are a large variety of other lipids. AFM-methods have been developed to study the Outer Membrane of Mycobacterium tuberculosis, which appears to be very smooth. However, individual mycobacterial cells are known to form strong clusters. Whereas the clustering process is apparent, the mechanism by which the stable aggregation of M. tuberculosis occurs is unknown and subject to various hypotheses.

We have discovered a porin from a related mycobacterium (MspA from Mycobacterium smegmatis) is able to reconstitute within the OM of Mycobacterium tuberculosis. This finding is of a special importance for future medical applications, because new pathways through the OM suggest a new way to successfully treat mycobacterial infections.