1887

Abstract

Mannose is an important constituent of the immunomodulatory glycoconjugates of the mycobacterial cell wall: lipoarabinomannan (LAM), lipomannan (LM) and the related phospho--inositol mannosides (PIMs). In and the related bacillus , mannose is either imported from the medium or derived from glycolysis, and is subsequently converted into the nucleotide-based sugar donor guanosine diphosphomannose (GDP-mannose). This can be utilized by the glycosyltranferases of the GT-A/B superfamily or converted to the lipid-based donor polyprenyl monophosphomannose, and used as a substrate by the transmembrane glycosyltransferases of the GT-C superfamily. To investigate GDP-mannose biosynthesis in detail, the gene encoding a putative ManC in was deleted. Deletion of resulted in a slow-growing mutant, with reduced but not totally abrogated guanosine diphosphomannose pyrophosphorylase activity. However, a comprehensive cell wall analysis revealed that Δ is deficient in PIMs and LM/LAM. Closer inspection suggests that promiscuous ManC activity is contributed by additional putative nucleotidyltransferases, PmmB, WbbL1, GalU and GlmU, and a hypothetical protein, NCgl0715. Furthermore, complementation analyses of Δ with Rv3264c suggested that it is a true homologue of ManC in , and the essentiality of PIMs in makes it an attractive drug target.

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2012-07-01
2019-10-15
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