The mycobacterial cell wall.

Abstract

The Mycobacterial cell wall contains a peptidoglycan—glycolipid complex and various more or less defined glycolipid fractions. The detailed chemical structure of the peptidoglycan and the glycolipid (a mycolate of an arabinogalactan) is discussed. Figure 4 shows a tentative formula for a 'monomer' of the cell wall and Figure 6 depicts a possible 'decamer.' Then the chemistry of three glycolipids which seem closely associated with the cell wall is reviewed: (1) Wax D of human strains is a mucopeptide-containing mycolate of arabinogalactan and is probably derived from the cell wall by enzymatic degradation as shown in Figure 6; (2) Cord factor is a dimycolate of trehalose (formula 22); (3) A newly defined suipholipid is a 2-sulphate of a tetra-acyl trehalose (formula 26). Other possible components of the cell wall are mentioned, such as the mycosides, a glucan and lipopeptides. Mass spectrometry has been a very helpful tool for defining the chemistry of all these compounds. Finally the biological activities of mycobacterial cell walls and their components are considered, such as: specific immunization against tuberculosis, adjuvant activity and stimulation of non-specific resistance to infections. In this lecture, I shall try to summarize our present knowledge of the chemistry of a very complex and most fascinating natural macromolecule: the cell wall of Mycobacteria and related organisms. 'Very complex' because we shall see that it contains lipids, peptides and carbohydrates. 'Fascinating' because there is a great deal of novel structural chemistry involved and new biosynthetic pathways to explore, and because many of the pathogenic effects of tubercie bacilli and related organisms are due to constituents of the cell wall. We shall be concerned not only with the insoluble macromolecular, rigid cell wall and its covalent chemical structure, but also with a series of soluble lipid compounds which seem to be located in or on the outer part of the cell wall, such as wax D, cord factor and sulpholipids. We shall start with a chemical study of the various structures, and shall see that mass spectrometry has been a most helpful tool for bringing precision and order into this most complex field, and we shall end this lecture with a rapid survey of the biological properties of mycobacterial cell walls. Animal experiments show indeed that preparations derived from mycobacterial cell walls have interesting properties concerning adjuvant activity, 135 E. LEDERER and the stimulation of non-specific resistance, which can be used not only against bacterial and viral infections, but also against certain types of leukaemia and cancer. I. CHEMICAL STRUCTURE OF THE MYCOBACTERIAL CELL WALL: A PEPTIDOGLYCAN GLYCOLIPID COMPLEX The two major components of the mycobacterial cell wall are: a peptidoglycan and a glycolipid (Kotani et al.1, Takeya et al.2, Misaki et al.3, Kanetsuna4). (1) The peptidoglycan (mucopeptide or murein)t Here we can distinguish the glycan backbone consisting of a repeating disaccharide unit and a peptide moiety. (a) The disaccharide unit The classical work of Ghuysen5' 6, Jeanloz7, Park8, Salton9 and Strominger1° has shown that the cell wall of all bacteria analysed so far contains a peptidoglycan having a glycan backbone of repeating disaccharide units of structure 1, where N-acetyl-D-glucosamine is linked in 31 —+ 4 to N-acetyl-D-muramic acid. The only variations found so far were that N-acetyl muramic acid is 6-O-acetylated in Staphylococcus aureus cell wall'1 and that muramic acid forms a lactame in certain bacterial spores1 2