Transcriptional regulation of lipid homeostasis in mycobacteria.

SALZMAN V; MONDINO S; SALA C; COLE ST; GAGO G; GRAMAJO H

MOLECULAR MICROBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2010 vol. 78 p. 64 - 77

0950-382X

Mycolic acids are major components of the cell enve-lope of mycobacteria, such as Mycobacterium tuber-culosis, 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 demonstratedin vitro andin vivo. Overexpression and knock-down studies in Mycobacterium smegmatisrevealed the repressor nature of MabR, with reduced amounts of FAS-II tran-scripts and fatty acids in the overproducing strain. Under these conditions, downregulation offas tran-scription was also observed, thereby suggesting the existence of cross-talk between the two FAS, medi-ated by MabR. Finally, the finding that amabRknock-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.