DISSECTING THE TRANSCRIPTIONAL REGULATION OF fas-acpS OPERON IN MYCOBACTERIA.

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

Rosario

Congreso; IV Congreso de Microbiología General (SAMIGE); 2013

SAMIGE

DISSECTING THE TRANSCRIPTIONAL REGULATION OF fas-acpS OPERON IN MYCOBACTERIA. 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, working in a coordinate manner to keep lipid homeostasis tightly regulated. Our leading studies on the regulation of fasII operon provided strong evidences of the existence of a sophisticated network that coordinates the activity of the two mycobacterial FAS systems at the transcriptional level. Following with these studies, we confirmed that fas and acpS form a single transcriptional unit named operon fas-acpS, and we identified a new transcriptional regulator of this operon, named FasR. This protein is able to activate fas-acpS expression through binding to three repeated sequences in the operon promoter region (Pfas). FasR binding and functionality are impaired by long chain acyl-CoAs, a modulatory effect confirmed by -galactosidase and EMSA assays. The construction and further characterization of a fasR conditional mutant in M. smegmatis demonstrated that this regulatory protein is essential for the bacterium viability and corroborated its activator nature in vivo. Because FasR is not present in eukaryotes or in the gut flora it results an attractive target for the development of new and specific antimycobacterial drugs against essential transcriptional regulators. Mondino, Sonia; Gramajo, Hugo and Gago, Gabriela. Instituto de Biología Molecular y Celular de Rosario. IBR-CONICET, Rosario-Argentina. E-mail: mondino@ibr-conicet.gov.ar