IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Characterization of a transcriptional regulator of mycolic acid biosynthesis in Mycobacterium tuberculosis
Autor/es:
TSAI, Y; SALZMAN, V; GAGO, G.; GRAMAJO, H
Lugar:
Rosario
Reunión:
Congreso; IV Congreso de Microbiología General (SAMIGE); 2013
Institución organizadora:
SAMIGE
Resumen:
Characterization of a transcriptional regulator of mycolic acid biosynthesis in Mycobacterium tuberculosis Mycolic acids, the dominant feature of Mycobacterium tuberculosis outer membrane, are essential for the survival, virulence and antibiotic exclusion of this human pathogen. Mycobacteria, unlike most bacteria, have two fatty acid synthases (FAS-I and FAS-II). Both of them are involved in the biosynthesis of mycolic acids. Our research group has identified MabR as a new transcriptional regulator that controls the expression of fasII operon genes, which encode for the enzymes of the FAS-II system, by binding specifically to the fasII promoter region. The construction and characterization of a MabR conditional mutant in M. smegmatis, allowed us to demonstrate that this protein modulates the expression of fasII genes in vivo. We also confirmed that MabR is essential to the regulatory network involved in the maintenance of lipid homeostasis. The results obtained in the mabR conditional mutant suggest that MabR is a transcriptional activator of the fasII operon genes. This result was supported by transcriptional fusion studies. We have also found that long chain acyl-CoAs or acyl-AcpM modulate the affinity of MabR for its DNA binding site, suggesting that these metabolites are sensed in vivo by MabR in order to keep the cellular lipid homeostasis by regulating the expression of the Fas-II system. MabR might become an excellent new target for the development of conceptually new antimycobacterial compounds as it is essential for the viability of this pathogen. Tsai, Yi Ting ; Salzman, Valentina; Gago, Gabriela and Gramajo, Hugo Instituto de Biología Molecular y Celular de Rosario. IBR-CONICET, Rosario-Argentina. E-mail: tsai@ibr-conicet.gov.ar