Glycopeptidolipids: Immuno‐modulators in greasy mycobacterial cell envelope

Abstract

SummarySpecies of opportunistic mycobacteria are the major causative agent for disseminating pulmonary infections in immunocompromised individuals. These naturally resistant strains recruit a unique type of glycolipid known as glycopeptidolipids (GPLs), noncovalently attached to the outer surface of their thick lipid rich cell envelope. Species specific GPLs constitute the chemical determinants of most nontuberculous mycobacterial serotypes, and their absence from the cell surface confers altered colony morphology, hydrophobicity, and inability to grow as biofilms. The objective of this review is to present a comprehensive account and highlight the renewed interest on this much neglected group of pleiotropic molecules with respect to their structural diversity and biosynthesis. In addition, the role of GPLs in mycobacterial survival, both intracellular and in the environment is also discussed. It also explores the possibility of identifying new targets for intervening Mycobacterium avium complex-related infections. These antigenic molecules have been considered to play a pivotal role in immune suppression and can also induce various cytokine mediated innate immune responses, the molecular mechanism of which remains obscure. IUBMBIUBMB Life, 64(3): 215-225, 2012

Mycobacterium massiliense Type II genotype leads to higher level of colony forming units and TNF‐α secretion from human monocytes than Type I genotype

“…Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis also supported GLP loss in the M. massiliense Type II genotype (data not shown), which may be due to the large deletions of GPL-related genes in its genome as reported previously (20). Given that mycobacterial cell wall GPL is one of the most important factors determining virulence, leading to the modulation of the host immune response (31,32), it is likely that two genotypes of M. massiliense would show different pathogenesis.…”

Structural determination of glycopeptidolipids of Mycobacterium smegmatis by high‐resolution multiple‐stage linear ion‐trap mass spectrometry with electrospray ionization

“…GPLs also play important roles in biofilm formation, cell invasion and immune modulation; and variations in GPL structure, for example, structural modifications of the carbohydrate moieties, may affect the pathogenicity of M. avium complex and other GPL‐expressing mycobacteria . The immunomodulation aspects of M. avium pathogenesis and the role of GPLs as virulence factors have been recently reviewed …”

Cloning, mutagenesis, and characterization of the microalga Parietochloris incisa acetohydroxyacid synthase, and its possible use as an endogenous selection marker

“…These genes, many in operons, are responsible for the synthesis of peptide core and fatty acid acyl chain, the modification of GPLs core (glycosylation, methylation, acetylation), the assembly of various synthesizing enzymes on the cell membrane and the export of GPLs, respectively. GPLs locus is around 65 kb in M. smegmatis [Ripoll et al, 2007; Mukherjee and Chatterji, 2012]. M. abscessus and M. chelonae have the GPLs locus similar to that of M. smegmatis , but the genes involved in synthesis of fatty acid chain are comparatively scattered.…”

“…It is believed that an Acyl‐CoA dehydrogenase (FadE5) incorporates an unsaturation into the fatty acyl chain generated by the fatty acid synthase system in mycobacteria (FAS I and FAS II), then this fatty acyl chain is extended and hydroxylated by the polyketide synthase Pks [Trivedi et al, 2004; Mukherjee and Chatterji, 2012]. The hydroxylated fatty acyl chain transferred from Pks to the peptide synthase (Mps), with the help of the polyketide synthase associated protein (PapA3), is attached to the tripeptidyl amino‐alcohol [Trivedi et al, 2004; Mukherjee and Chatterji, 2012; Tatham et al, 2012]. Mps identified by Billman‐Jacobe and his colleagues in 1999 from the Tn insertion mutant library of M. smegmatis consists of four function modules responsible for the formation of tripeptidyl amino alcohol skeleton.…”

“…The first three modules with racemase activity generate the D configuration of the target amino acids and add these D form amino acids to the fatty acyl chain. The module IV without racemase activity incorporates a L ‐alanine into the tripeptide D ‐Phe‐ D ‐ allo Thr‐ D ‐Ala and further reduces this L ‐alanine to a L ‐alaninol [Billman‐Jacobe et al, 1999; Mukherjee and Chatterji, 2012]. The above enzymes synergize to form the lipopeptide core.…”