title: Transcriptional regulation of lipid homeostasis in mycobacteria.
abstract: Mycolic acids are major components of the cell envelope of mycobacteria, such as Mycobacterium tuberculosis, and play an important role in its architecture, impermeability and interaction with the environment. Synthesis of mycolic acids is carried out by two types of fatty acid synthases (FAS) working in concert: type I FAS, a multifunctional enzyme capable of de novo synthesis of medium-chain fatty acids, and type II FAS, responsible for their elongation. In this article we report the identification and characterization of a transcriptional regulator (MabR), whose binding to the FAS-II promoter region was demonstrated in vitro and in vivo. Overexpression and knock-down studies in Mycobacterium smegmatis revealed the repressor nature of MabR, with reduced amounts of FAS-II transcripts and fatty acids in the overproducing strain. Under these conditions, downregulation of fas transcription was also observed, thereby suggesting the existence of cross-talk between the two FAS, mediated by MabR. Finally, the finding that a mabR knock-out mutant could only be obtained in a merodiploid strain of M. smegmatis, confirmed the predicted essentiality, thus implying an essential role for MabR in mycobacterial fatty acid metabolism.
authors.affiliation: Microbiology Division, Instituto de Biología Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531 (S2002LRK) Rosario, Argentina.
authors.forename: V
authors.initials: V
authors.lastname: Salzman
authors.forename: S
authors.initials: S
authors.lastname: Mondino
authors.forename: C
authors.initials: C
authors.lastname: Sala
authors.forename: S T
authors.initials: ST
authors.lastname: Cole
authors.forename: G
authors.initials: G
authors.lastname: Gago
authors.forename: H
authors.initials: H
authors.lastname: Gramajo
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D054889:Fatty Acid Synthase, Type II / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis*; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator; D050356:Lipid Metabolism; D020102:Mycobacterium smegmatis / Q000201:enzymology / Q000235:genetics*; D009876:Operon; D011401:Promoter Regions, Genetic
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids; D054889:Fatty Acid Synthase, Type II