The surface glycopeptidolipids of mycobacteria: structures and biological properties

Abstract

One of the most important opportunistic pathogens associated with acquired immunodeficiency syndrome (AIDS) is the M. avium complex. M. avium infections are found in up to 70% of individuals in advanced stages of AIDS. It is apparent that M. avium can replicate in host macrophages and persist for long periods. This group of mycobacteria are distinguished by the presence of unique, highly antigenic, surface-located lipids known as the glycopeptidolipids (GPLs). The GPLs are the chemical basis of the 31 distinct serovars of the M. avium complex, and have also been identified in some other species. The M. avium lipids are immunosuppressive and can induce a variety of cytokines that affect general host responses. Despite extensive chemical characterization of the structures of these GPLs, much work is needed to elucidate the molecular mechanism involved in this complex glycosylation pathway and its genetic basis. The challenges for the future lie in explaining the roles of these copious products in the intracellular life and infectivity of mycobacteria. The intention of our review is to offer a concise account of the structures of the M. avium lipids, their putative roles in the host responses, bacterial physiology and pathogenesis, particularly in immunocompromised patients such as those infected with human immunodeficiency virus (HIV). Advances in chemical synthesis of the various haptenic oligosaccharides are also given to demonstrate how these have helped to define the immunogenic determinants. We believe that future research should involve the creation of conditional mutants defective in these lipids for both functional and biosynthesis studies which will complement biological assays using chemically defined or modified neoglycoconjugates.

Surface-exposed Glycopeptidolipids of Mycobacterium smegmatis Specifically Inhibit the Phagocytosis of Mycobacteria by Human Macrophages

“…These simplest forms are found in all GPL-containing mycobacterial species and, accordingly, are called non-servar-specific GPLs or apolar GPLs. The allo-threoninyl-linked sugar unit of non-servar-specific GPLs may be further glycosylated in some GPL-containing mycobacteria, such as M. avium (33,34). These discrete modifications confer to GPLs variable TLC patterns and antigenic properties (20,33,34).…”

Modification of glycopeptidolipids by an O-methyltransferase of Mycobacterium smegmatis a aThe GenBank accession number for the sequence determined in this work is AY138899.

“…et al, 1983). Studies have shown that GPLs of M. avium are immunosuppressive and induce some cytokines, thus affecting the host's response to infection (Chatterjee & Khoo, 2001 ;Horgen et al, 2000). Most mycobacterial Abbreviations : DIG, digoxigenin ; ESI-MS, electrospray ionization mass spectrometry ; GPL, glycopeptidolipid ; HPTLC, high-performance thin-layer chromatography.…”

Phylogeny of Mycobacterium avium strains inferred from glycopeptidolipid biosynthesis pathway genes

“…However, GPLs of serotype 10 and 11 have been shown to be identical by GC-MS and ELISA . Another distinct characteristic of the ssGPLs that is shared by all three PCR-negative M. avium serotypes is a unique component that allows attachment of haptenic oligosaccharide to the N-acylpeptide core (Chatterjee & Khoo, 2001). We suggest that the lack of genes used as markers in the present study reflects an altered genetic basis for the ssGPL biosynthesis in these strains.…”

“…With the exception of serotypes 5, 10 and 11, which are distinguished by the 3-O-Mea-L-Rhap-(1R2)-dTal component, this unit is present in all serotypes, serving as a core to which the next sugar is added during oligosaccharide chain elongation (Chatterjee & Khoo, 2001). Insertional inactivation by a mobile element or deletion of the gene responsible for the addition of that sugar would lead to the formation of the serotype 1 GPL, regardless of the presence of genes encoding enzymes necessary for further modification of the GPL.…”

“…Two forms of GPLs are present in MAC, the serotypespecific GPL (ssGPL) and non-serotype specific GPL (nsGPL) (for a review, see Chatterjee & Khoo, 2001). All GPLs have in common an N-acylated lipotetrapeptide core that bears a rhamnosylated alaninyl C terminus.…”