IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Regulatory network in mycobacteria: key role of long chain acyl-CoAs.
Autor/es:
LARA, J; TSAI, Y; MONDINO, S; GAGO, G.; GRAMAJO, H
Lugar:
La Plata
Reunión:
Congreso; 8th International Conference on Lipid Binding Proteins; 2013
Resumen:
REGULATORY NETWORK IN MYCOBACTERIA: KEY ROLE OF LONG CHAIN ACYL-COAS Julia Lara, Yi-Ting Tsai, Valentina Salzman, Sonia Mondino, Gabriela Gago and Hugo Gramajo Instituto de Biología Molecular y Celular de Rosario. IBR-CONICET, Rosario - Argentina. lara@ibr-conicet.gov.ar Mycolic acids (MA), one of the most important lipids of the outer membrane of mycobacteria, have been largely associated with bacterial virulence and antibiotic resistance and its biosynthesis pathway is one of the main targets for TB treatment. Biosynthesis of MA involves two fatty acid synthase systems, FAS-I and FAS-II, which should work in a finely coordinate manner to keep lipid homeostasis tightly regulated. The main purpose of our studies is to understand how mycobacteria exert this exquisite control over the biosynthesis of their membrane lipids and find out the key components of the regulatory network that control lipid biosynthesis at the transcriptional level. We found that the expression of the fasII operon is regulated at the transcriptional level by MabR. This protein binds to an operator sequence present in the fasII promoter region, modulating in this way the biosynthesis of MA. Interestingly, overexpression of MabR not only affects the expression of fasII genes but also of fasI, providing strong evidences of the existence of a sophisticated regulatory network involved in the coordinate regulation of the two mycobacterial FAS systems at the transcriptional level. More recently, we characterized FasR, a new regulatory protein that specifically binds specifically binds to fas promoter region and controls the de novo fatty acid biosynthesis in mycobacteria. In this work, we present evidences that long-chain acyl-CoAs are key effector molecules that coordinate the expression of the two FAS systems at the transcriptional level, by directly binding to FasR and MabR. A better understanding of this complex process of regulation of lipid homeostasis in mycobacteria together with the structural characterization of these novel transcriptional regulators will greatly contribute to the development of new strategies to control this disease, including the design or identification of compounds that could deregulate fatty acid biosynthesis and induce bacterial death.