title: Deletion of manC in Corynebacterium glutamicum results in a phospho-myo-inositol mannoside- and lipoglycan-deficient mutant.
abstract: Mannose is an important constituent of the immunomodulatory glycoconjugates of the mycobacterial cell wall: lipoarabinomannan (LAM), lipomannan (LM) and the related phospho-myo-inositol mannosides (PIMs). In Mycobacterium tuberculosis and the related bacillus Corynebacterium glutamicum, 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 C. glutamicum was deleted. Deletion of manC resulted in a slow-growing mutant, with reduced but not totally abrogated guanosine diphosphomannose pyrophosphorylase activity. However, a comprehensive cell wall analysis revealed that C. glutamicumΔmanC 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 C. glutamicumΔmanC with Rv3264c suggested that it is a true homologue of ManC in M. tuberculosis, and the essentiality of PIMs in M. tuberculosis makes it an attractive drug target.
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Mishra
authors.affiliation: Biotechnology (IBG-1), Research Centre Juelich GmbH, D-52425 Juelich, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Krumbach
authors.affiliation: Biotechnology (IBG-1), Research Centre Juelich GmbH, D-52425 Juelich, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Rittmann
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Batt
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Oona Y-C
authors.initials: OY
authors.lastname: Lee
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Sandip
authors.initials: S
authors.lastname: De
authors.affiliation: Biotechnology (IBG-1), Research Centre Juelich GmbH, D-52425 Juelich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Frunzke
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.affiliation: Biotechnology (IBG-1), Research Centre Juelich GmbH, D-52425 Juelich, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Eggeling
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D048230:Corynebacterium glutamicum / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D017353:Gene Deletion; D005816:Genetic Complementation Test; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics; D010716:Phosphatidylinositols / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; C034154:phosphatidylinositol mannoside