title: Genetic basis for the biosynthesis of methylglucose lipopolysaccharides in Mycobacterium tuberculosis.
abstract: Mycobacteria produce two unusual polymethylated polysaccharides, the 6-O-methylglucosyl-containing lipopolysaccharides (MGLP) and the 3-O-methylmannose polysaccharides, which have been shown to regulate fatty acid biosynthesis in vitro. A cluster of genes dedicated to the synthesis of MGLP was identified in Mycobacterium tuberculosis and Mycobacterium smegmatis. Overexpression of the putative glycosyltransferase gene Rv3032 in M. smegmatis greatly stimulated MGLP production, whereas the targeted disruption of Rv3032 in M. tuberculosis and that of the putative methyltransferase gene MSMEG2349 in M. smegmatis resulted in a dramatic reduction in the amounts of MGLP synthesized and in the accumulation of precursors of these molecules. Disruption of Rv3032 also led to a significant decrease in the glycogen content of the tubercle bacillus, indicating that the product of this gene is likely to be involved in the elongation of more than one alpha-(1-->4)-glucan in this bacterium. Results thus suggest that Rv3032 encodes the alpha-(1-->4)-glucosyltransferase responsible for the elongation of MGLP, whereas MSMEG2349 encodes the O-methyltransferase required for the 6-O-methylation of these compounds.
authors.affiliation: UnitédeGénétique Mycobactérienne Institut Pasteur, 75015 Paris, France.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Stadthagen
authors.affiliation: Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale, CNRS, 31077 Toulouse, France.
authors.forename: Tounkang
authors.initials: T
authors.lastname: Sambou
authors.affiliation: Unité de Biochimie Structurale, Institut Pasteur, 75015 Paris, France and the.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Guerin
authors.affiliation: UnitédeGénétique Mycobactérienne Institut Pasteur, 75015 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Barilone
authors.affiliation: UnitédeGénétique Mycobactérienne Institut Pasteur, 75015 Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Boudou
authors.affiliation: UnitédeGénétique Mycobactérienne Institut Pasteur, 75015 Paris, France.
authors.forename: Jana
authors.initials: J
authors.lastname: Korduláková
authors.affiliation: UnitédeGénétique Mycobactérienne Institut Pasteur, 75015 Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Charles
authors.affiliation: Unité de Biochimie Structurale, Institut Pasteur, 75015 Paris, France and the.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Alzari
authors.affiliation: Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale, CNRS, 31077 Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Lemassu
authors.affiliation: Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale, CNRS, 31077 Toulouse, France.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffé
authors.affiliation: Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale, CNRS, 31077 Toulouse, France.
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
authors.affiliation: UnitédeGénétique Mycobactérienne Institut Pasteur, 75015 Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.affiliation: Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale, CNRS, 31077 Toulouse, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Rivière
authors.affiliation: UnitédeGénétique Mycobactérienne Institut Pasteur, 75015 Paris, France. Electronic address: Mary.Jackson@colostate.edu.
authors.forename: Mary
authors.initials: M
authors.lastname: Jackson
mesh_terms: D006003:Glycogen / Q000032:analysis; D016695:Glycosyltransferases / Q000235:genetics / Q000502:physiology; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D008757:Methylglucosides / Q000032:analysis*; D005810:Multigene Family; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D008070:Lipopolysaccharides; D008757:Methylglucosides; C033884:6-O-methylglucose; D006003:Glycogen; D016695:Glycosyltransferases