Deciphering sulfoglycolipids of Mycobacterium tuberculosis

Autor: Diane Cala-De Paepe, Gerald Larrouy-Maumus, Germain Puzo, Martine Gilleron, Sathish Mundayoor, Buko Lindner, Emilie Layre, Julien Vaubourgeix
Přispěvatelé: Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Mycobacteria Research Group, Department of Molecular Microbiology, Rajiv Gandhi Centre for Biotechnology, Thycaud Post, Thiruvananthapuram, Kerala 695 014, India, Mycobacteria research group, Rajiv Gandhi Centre for Biotechnology (RGCB)-Rajiv Gandhi Centre for Biotechnology (RGCB)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Journal of Lipid Research
Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2011, 52 (6), pp.1098-1110. ⟨10.1194/jlr.M013482⟩
Journal of Lipid Research, Vol 52, Iss 6, Pp 1098-1110 (2011)
ISSN: 0022-2275
DOI: 10.1194/jlr.M013482⟩
Popis: 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.
Databáze: OpenAIRE