Trafficking pathways of mycolic acids: structures, origin, mechanism of formation, and storage form of mycobacteric acids.
Mycolic acids, the hallmark of mycobacteria and related bacteria, are major and specific components of their cell envelope and essential for the mycobacterial survival. Mycobacteria contain structurally related long-chain lipids, but the metabolic relationships between these various classes of compounds remain obscure. To address this question a series of C(35) to C(54) nonhydroxylated fatty acids (mycobacteric acids), ketones, and alcohols structurally related to the C(70-80) dicyclopropanated or diethylenic mycolic acids were characterized in three mycobacterial strains and their structures compared. The relationships between these long-chain acids and mycolic acids were established by following the in vivo traffic of (14)C labeled alpha-mycolic acids purified from the same mycobacterial species. The labeling was exclusively found in mycobacteric acids. The mechanism of this degradation was established by incorporation of (18)O(2) into long-chain lipids and shown to consist in the rupture of mycolic acids between carbon 3 and 4 by a Baeyer-Villiger-like reaction. We also demonstrated that mycobacteric acids occur exclusively in the triacylglycerol (TAG) fraction where one molecule of these acids esterifies one of the three hydroxyl groups of glycerol. Altogether, these data suggest that these compounds represent a pathway of metabolic energy that would be used by mycobacteria in particular circumstances.
Rafidinarivo
Elie
E
Present address of E. Rafidinarivo: Ecole Normale Niveau III, B.P. 881, 101 Antananarivo, Madagascar; Université Paul Sabatier (Toulouse III), Institut de Pharmacologie et Biologie Structurale (IPBS), 205 route de Narbonne, 31077 Toulouse Cedex, France; Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5089), IPBS, Department 'Mécanismes Moléculaires des Infections Mycobactériennes,' 205 route de Narbonne, 31077 Toulouse Cedex, France.
Lanéelle
Marie-Antoinette
MA
Université Paul Sabatier (Toulouse III), Institut de Pharmacologie et Biologie Structurale (IPBS), 205 route de Narbonne, 31077 Toulouse Cedex, France; Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5089), IPBS, Department 'Mécanismes Moléculaires des Infections Mycobactériennes,' 205 route de Narbonne, 31077 Toulouse Cedex, France.
Montrozier
Henri
H
Université Paul Sabatier (Toulouse III), Institut de Pharmacologie et Biologie Structurale (IPBS), 205 route de Narbonne, 31077 Toulouse Cedex, France; Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5089), IPBS, Department 'Mécanismes Moléculaires des Infections Mycobactériennes,' 205 route de Narbonne, 31077 Toulouse Cedex, France.
Valero-Guillén
Pedro
P
Departamento de Genética y Microbiologia, Facultad de Medicina y Odontologia, Universidad de Murcia, 30100 Murcia, Spain.
Astola
José
J
Departament de Genètica y Microbiologia, Facultat de Ciences, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain.
Luquin
Marina
M
Departament de Genètica y Microbiologia, Facultat de Ciences, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain.
Promé
Jean-Claude
JC
Université Paul Sabatier (Toulouse III), Institut de Pharmacologie et Biologie Structurale (IPBS), 205 route de Narbonne, 31077 Toulouse Cedex, France; Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5089), IPBS, Department 'Mécanismes Moléculaires des Infections Mycobactériennes,' 205 route de Narbonne, 31077 Toulouse Cedex, France.
Daffé
Mamadou
M
Université Paul Sabatier (Toulouse III), Institut de Pharmacologie et Biologie Structurale (IPBS), 205 route de Narbonne, 31077 Toulouse Cedex, France; Departamento de Genética y Microbiologia, Facultad de Medicina y Odontologia, Universidad de Murcia, 30100 Murcia, Spain. Electronic address: mamadou.daffe@ipbs.fr.
D004734:Energy Metabolism; D005227:Fatty Acids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D015394:Molecular Structure; D009161:Mycobacterium / Q000254:growth & development / Q000378:metabolism*; D009171:Mycolic Acids / Q000737:chemistry* / Q000378:metabolism*; D010103:Oxygen Isotopes; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D005227:Fatty Acids; D009171:Mycolic Acids; D010103:Oxygen Isotopes; C013596:meromycolic acids