title: Mycobacterium tuberculosis Is a Natural Ornithine Aminotransferase (rocD) Mutant and Depends on Rv2323c for Growth on Arginine.
abstract: Mycobacterium tuberculosis (Mtb) possesses a genetic repertoire for metabolic pathways, which are specific and fit to its intracellular life style. Under in vitro conditions, Mtb is known to use arginine as a nitrogen source, but the metabolic pathways for arginine utilization have not been identified. Here we show that, in the presence of arginine, Mtb upregulates a gene cluster which includes an ornithine aminotransferase (rocD) and Rv2323c, a gene of unknown function. Isotopologue analysis by using 13C- or 15N-arginine revealed that in Mtb arginine is not only used as nitrogen source but also as carbon source for the formation of amino acids, in particular of proline. Surprisingly, rocD, which is widespread in other bacteria and is part of the classical arginase pathway turned out to be naturally deleted in Mtb, but not in non-tuberculous mycobacteria. Mtb lacking Rv2323c showed a growth defect on arginine, did not produce proline from arginine, and incorporated less nitrogen derived from arginine in its core nitrogen metabolism. We conclude that the highly induced pathway for arginine utilization in Mtb differs from that of other bacteria including non-tuberculous mycobacteria, probably reflecting a specific metabolic feature of intracellular Mtb.
authors.affiliation: Department of Medical Microbiology and Hospital Epidemiology, Medical School Hannover, 30625 Hanover, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Hampel
authors.affiliation: Lehrstuhl für Biochemie, Technische Universität München, Garching, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Huber
authors.affiliation: Research Group Genome Analytics, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.affiliation: Lehrstuhl für Biochemie, Technische Universität München, Garching, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Spona-Friedl
authors.affiliation: Lehrstuhl für Biochemie, Technische Universität München, Garching, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eisenreich
authors.affiliation: Department of Medical Microbiology and Hospital Epidemiology, Medical School Hannover, 30625 Hanover, Germany.
authors.forename: Franz-Christoph
authors.initials: FC
authors.lastname: Bange
mesh_terms: D001120:Arginine / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics*; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D009953:Ornithine-Oxo-Acid Transaminase / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D001120:Arginine; D009953:Ornithine-Oxo-Acid Transaminase