FasR, a novel transcriptional activator of the fas gene of Mycobacterium tuberculosis.

MONDINO, SONIA; GRAMAJO, H; GAGO, G.

POTRERO DE LOS FUNES-SAN LUIS

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011

SAIB

FasR, a novel transcriptional activator of the fas gene of Mycobacterium tuberculosis. Mondino, Sonia; Gramajo, Hugo and Gago, Gabriela. Instituto de Biología Molecular y Celular de Rosario. IBR-CONICET, Rosario-Argentina. E-mail: mondino@ibr.gov.ar M. tuberculosis remains a major human public health threat. The success of this pathogen largely stems from its remarkable capacity to survive within the infected host, being its unusual cell wall a key factor in this survival. Mycobacteria cell wall biosynthesis involves two structural distinct fatty acid synthase systems, FAS-I and FAS-II, which should work in a finely coordinate manner to keep lipid homeostasis tightly regulated. Our studies on the regulation of the fasII operon provided strong evidences of the existence of a sophisticated regulatory signalling cascade involved in the coordinate regulation of the mycobacterial FAS systems at the transcriptional level. Recently, we were able to identify and purify from M. smegmatis crude extracts, a new transcriptional regulator of the fas gene, named FasR. Footprinting assays demonstrated that FasR specifically recognize two regions in the fas gene promoter (pfas). The interaction of FasR with pfas is inhibited in the presence of long chain acyl-CoAs. Beta-galactosidase assays indicated that FasR is a positive regulator of fas gene and confirmed the modulatory role of long chain acyl-CoAs in the transcription of the fas gene. Construction of the mutant strain will help us to elucidate the complex regulatory network of fatty acids biosynthetic pathway, an attractive target for the development of new antimycobacterial drugs.