The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan

doi:10.1101/cshperspect.a021113

Review

. 2015 Mar 27;5(8):a021113.

doi: 10.1101/cshperspect.a021113.

The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan

Luke J Alderwick¹, James Harrison¹, Georgina S Lloyd¹, Helen L Birch¹

Affiliations

PMID: 25818664
PMCID: PMC4526729
DOI: 10.1101/cshperspect.a021113

Review

The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan

Luke J Alderwick et al. Cold Spring Harb Perspect Med. 2015.

. 2015 Mar 27;5(8):a021113.

doi: 10.1101/cshperspect.a021113.

Authors

Luke J Alderwick¹, James Harrison¹, Georgina S Lloyd¹, Helen L Birch¹

Affiliation

¹ Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.

PMID: 25818664
PMCID: PMC4526729
DOI: 10.1101/cshperspect.a021113

Abstract

The mycobacterial bacillus is encompassed by a remarkably elaborate cell wall structure. The mycolyl-arabinogalactan-peptidoglycan (mAGP) complex is essential for the viability of Mycobacterium tuberculosis and maintains a robust basal structure supporting the upper "myco-membrane." M. tuberculosis peptidoglycan, although appearing to be unexceptional at first glance, contains a number of unique molecular subtleties that become particularly important as the TB-bacilli enters into nonreplicative growth during dormancy. Arabinogalactan, a highly branched polysaccharide, serves to connect peptidoglycan with the outer mycolic acid layer, and a variety of unique glycolsyltransferases are used for its assembly. In this review, we shall explore the microbial chemistry of this unique heteropolysacchride, examine the molecular genetics that underpins its fabrication, and discuss how the essential biosynthetic process might be exploited for the development of future anti-TB chemotherapies.

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References

1. Adam A, Petit JF, Wietzerbin-Falszpan J, Sinay P, Thomas DW, Lederer E. 1969. L’acide N-glycolylmuramique, constituant des parois de Mycobacterium smegmatis: Identification par spectrometrie de masse. FEBS Lett 4: 87–92. - PubMed
1. Alderwick LJ, Radmacher E, Seidel M, Gande R, Hitchen PG, Morris HR, Dell A, Sahm H, Eggeling L, Besra GS. 2005. Deletion of Cg-emb in Corynebacterianeae leads to a novel truncated cell wall arabinogalactan, whereas inactivation of Cg-ubiA results in an arabinan-deficient mutant with a cell wall galactan core. J Biol Chem 280: 32362–32371. - PubMed
1. Alderwick LJ, Dover LG, Seidel M, Gande R, Sahm H, Eggeling L, Besra GS. 2006a. Arabinan-deficient mutants of Corynebacterium glutamicum and the consequent flux in decaprenylmonophosphoryl-d-arabinose metabolism. Glycobiology 16: 1073–1081. - PubMed
1. Alderwick LJ, Seidel M, Sahm H, Besra GS, Eggeling L. 2006b. Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J Biol Chem 281: 15653–15661. - PubMed
1. Alderwick LJ, Dover LG, Veerapen N, Gurcha SS, Kremer L, Roper DL, Pathak AK, Reynolds RC, Besra GS. 2008. Expression, purification and characterisation of soluble GlfT and the identification of a novel galactofuranosyltransferase Rv3782 involved in priming GlfT-mediated galactan polymerisation in Mycobacterium tuberculosis. Protein Expr Purif 58: 332–341. - PubMed

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[1] Adam A, Petit JF, Wietzerbin-Falszpan J, Sinay P, Thomas DW, Lederer E. 1969. L’acide N-glycolylmuramique, constituant des parois de Mycobacterium smegmatis: Identification par spectrometrie de masse. FEBS Lett 4: 87–92. - PubMed

[2] Adam A, Petit JF, Wietzerbin-Falszpan J, Sinay P, Thomas DW, Lederer E. 1969. L’acide N-glycolylmuramique, constituant des parois de Mycobacterium smegmatis: Identification par spectrometrie de masse. FEBS Lett 4: 87–92. - PubMed

[3] Alderwick LJ, Radmacher E, Seidel M, Gande R, Hitchen PG, Morris HR, Dell A, Sahm H, Eggeling L, Besra GS. 2005. Deletion of Cg-emb in Corynebacterianeae leads to a novel truncated cell wall arabinogalactan, whereas inactivation of Cg-ubiA results in an arabinan-deficient mutant with a cell wall galactan core. J Biol Chem 280: 32362–32371. - PubMed

[4] Alderwick LJ, Radmacher E, Seidel M, Gande R, Hitchen PG, Morris HR, Dell A, Sahm H, Eggeling L, Besra GS. 2005. Deletion of Cg-emb in Corynebacterianeae leads to a novel truncated cell wall arabinogalactan, whereas inactivation of Cg-ubiA results in an arabinan-deficient mutant with a cell wall galactan core. J Biol Chem 280: 32362–32371. - PubMed

[5] Alderwick LJ, Dover LG, Seidel M, Gande R, Sahm H, Eggeling L, Besra GS. 2006a. Arabinan-deficient mutants of Corynebacterium glutamicum and the consequent flux in decaprenylmonophosphoryl-d-arabinose metabolism. Glycobiology 16: 1073–1081. - PubMed

[6] Alderwick LJ, Dover LG, Seidel M, Gande R, Sahm H, Eggeling L, Besra GS. 2006a. Arabinan-deficient mutants of Corynebacterium glutamicum and the consequent flux in decaprenylmonophosphoryl-d-arabinose metabolism. Glycobiology 16: 1073–1081. - PubMed

[7] Alderwick LJ, Seidel M, Sahm H, Besra GS, Eggeling L. 2006b. Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J Biol Chem 281: 15653–15661. - PubMed

[8] Alderwick LJ, Seidel M, Sahm H, Besra GS, Eggeling L. 2006b. Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J Biol Chem 281: 15653–15661. - PubMed

[9] Alderwick LJ, Dover LG, Veerapen N, Gurcha SS, Kremer L, Roper DL, Pathak AK, Reynolds RC, Besra GS. 2008. Expression, purification and characterisation of soluble GlfT and the identification of a novel galactofuranosyltransferase Rv3782 involved in priming GlfT-mediated galactan polymerisation in Mycobacterium tuberculosis. Protein Expr Purif 58: 332–341. - PubMed

[10] Alderwick LJ, Dover LG, Veerapen N, Gurcha SS, Kremer L, Roper DL, Pathak AK, Reynolds RC, Besra GS. 2008. Expression, purification and characterisation of soluble GlfT and the identification of a novel galactofuranosyltransferase Rv3782 involved in priming GlfT-mediated galactan polymerisation in Mycobacterium tuberculosis. Protein Expr Purif 58: 332–341. - PubMed

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The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan

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The Mycobacterial Cell Wall--Peptidoglycan and Arabinogalactan

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