The role of the N-glycolyl modification in Mycobacterial peptidoglycan synthesis and survival

Mycobacteria are acid fast bacilli responsible for the wide spread global diseases tuberculosis and leprosy. The increased persistence of multidrug resistant (MDR) mycobacterial strains has led to the focus on discovery of new and under-utilised cellular targets such as the cell wall. Peptidoglycan, the principle structural component of the bacterial cell wall is a heteropolymer comprised of alternating monosaccharides cross-linked by pentapeptide chains. The cell wall of mycobacteria are inherently resistant to antimicrobials and aid in evasion from host immune detection due to modifications to its composition. The hydroxylase enzyme NamH has been documented to play a role in the N-glycolylation of peptidoglycan monosaccharides, utilizing molecular oxygen during aerobic growth to convert N-acetylto N-glycolyl groups. This modification is found predominantly in Actinobacteria, except Mycobacterium leprae due to genomic reduction. The percentage incorporation of Nacetylated and N-glycolylated saccharides is dependent upon the environment and functional characterisation of the impact of each modification is vital to achieving a greater understanding into mycobacterial response to a range of factors including ... (continues)