The Mycobacterial Cell Wall-Peptidoglycan and Arabinogalactan

The mycobacterial bacillus is encompassed by a remarkably elaborate cell wall structure. The mycolyl-arabinogalactan-peptidoglycan (mAGP) complex is essential for the viability of Mycobacterium tuberculosis and maintains a robust basal structure supporting the upper myco-membrane. M. tuberculosis peptidoglycan, although appearing to be unexceptional at first glance, contains a number of unique molecular subtleties that become particularly important as the TB-bacilli enters into nonreplicative growth during dormancy. Arabinogalactan, a highly branched polysaccharide, serves to connect peptidoglycan with the outer mycolic acid layer, and a variety of unique glycolsyltransferases are used for its assembly. In this review, we shall explore the microbial chemistry of this unique heteropolysacchride, examine the molecular genetics that underpins its fabrication, and discuss how the essential biosynthetic process might be exploited for the development of future anti-TB chemotherapies.