title: Deciphering sulfoglycolipids of Mycobacterium tuberculosis.
abstract: For 4 decades, in vivo and in vitro studies have suggested that sulfoglycolipids (SGLs) play a role in the virulence or pathogenesis of the tubercle bacilli. However, the SGL structure and biosynthesis pathway remain only partially elucidated. Using the modern tools of structural analysis, including MALDI-time-of-flight MS, MS/MS, and two-dimensional NMR, we reevaluated the structure of the different SGL acyl (di-, tri-, and tetra-acylated) forms of the reference strain Mycobacterium tuberculosis H37Rv, as well as those produced by the mmpL8 knockout strains previously described to intracellularly accumulate di-acylated SGL. We report here the identification of new acyl forms: di-acylated SGL esterified by simple fatty acids only, as well as mono-acylated SGL bearing a hydroxyphthioceranoic acid, which were characterized in the wild-type strain. In a clinical strain, a complete family of mono-acylated SGLs was characterized in high abundance for the first time. For the mmpL8 mutant, SGLs were found to be esterified i) by an oxophthioceranoic acid, never observed so far, and ii) at nonconventional positions in the case of the unexpected tri-acylated forms. Our results further confirm the requirement of MmpL8 for the complete assembly of the tetra-acylated forms of SGL and also provide, by the discovery of new intermediates, insights in terms of the possible SGL biosynthetic pathways.
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne, F-31077, Toulouse, France; UPS, Université de Toulouse, UPS; IPBS; F-31077 Toulouse, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Layre
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne, F-31077, Toulouse, France; UPS, Université de Toulouse, UPS; IPBS; F-31077 Toulouse, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Cala-De Paepe
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne, F-31077, Toulouse, France; UPS, Université de Toulouse, UPS; IPBS; F-31077 Toulouse, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Larrouy-Maumus
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne, F-31077, Toulouse, France; UPS, Université de Toulouse, UPS; IPBS; F-31077 Toulouse, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Vaubourgeix
authors.affiliation: Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India.
authors.forename: Sathish
authors.initials: S
authors.lastname: Mundayoor
authors.affiliation: Division of Biophysics, Research Center Borstel, Center for Medicine and Biosciences, Borstel, Germany.
authors.forename: Buko
authors.initials: B
authors.lastname: Lindner
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne, F-31077, Toulouse, France; UPS, Université de Toulouse, UPS; IPBS; F-31077 Toulouse, France.
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
authors.affiliation: CNRS; IPBS (Institut de Pharmacologie et de Biologie Structurale); 205 route de Narbonne, F-31077, Toulouse, France; UPS, Université de Toulouse, UPS; IPBS; F-31077 Toulouse, France. Electronic address: Martine.Gilleron@ipbs.fr.
authors.forename: Martine
authors.initials: M
authors.lastname: Gilleron
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism; D055786:Gene Knockout Techniques; D006017:Glycolipids / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D030781:Organisms, Genetically Modified / Q000378:metabolism* / Q000382:microbiology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014376:Tuberculosis / Q000382:microbiology*; D014774:Virulence
chemical_list: D005227:Fatty Acids; D006017:Glycolipids; C011117:sulfoglycolipids; D000217:Acyltransferases