M

"t

O-Palmitate O-Tuberculostearate

Figure 3 Schematic representation of mycobacterial lipoarabinomannan (LAM).

Mycolic Acids

Arabinogalactan

Peptidoglycan Plasma Membrane

Figure 4 Schematic drawing of the mycolyl-AG complex.

Figure 4 Schematic drawing of the mycolyl-AG complex.

toplasmic membrane. The tight packing of these chains results in very low fluidity of the cell wall, which in some cases is essentially crystalline [30,31]. The fluidity is dependent on the mycolic acids present, which in turn are species specific [31]. However, in all cases a major problem in treating mycobacterial infections is the passage of drugs through this lipid barrier into the host.

This model was initially criticized by some, who suggested that the AG was too large to accommodate the tight packing of the lipid chains [28]. However, a more detailed look at the structure of the AG provides a solution to this problem. A distinguishing feature of mycobacterial AG is the almost exclusive presence of furanosyl (Ara/or Gal/) residues. Furanoside rings are known to be much less conformationally well defined than their pyranoside counterparts [32]. It has been suggested that this inherent increased flexibility, in addition to the predominant coupling of these residues through linkages that involve primary hydroxyl groups, results in the poly-saccharide being a scaffold of high flexibility. This in turn allows the polymer to adopt a conformation that facilitates the orientation of the mycolic acids into tightly packed parallel arrays. Additionally, this proposal provides a reasonable explanation for what, from an evolutionary standpoint, seems odd. Polysaccharides containing furanosyl residues are expected to be less thermodynamically stable than those possessing pyranose rings, and it therefore appears that these organisms have developed a system whereby glycan stability is traded for the protection afforded by the tightly packed mycolic acids.

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