Characterization of a transcriptional regulator of mycolic acid biosynthesis in mycobacterium

VALENTINA SALZMAN; SONIA MONDINO; GABRIELA GAGO; HUGO C GRAMAJO

Carlos Paz, Córdoba, Argentina

Congreso; XLIV Reunión anual de la Sociedad Argentina de Investigación en Bioquímica y Biología molecular; 2008

SAIB

The most relevant lipids present in Mycobacterium cell envelope are mycolic acids. These unusual fatty acids are essential for the survival and virulence of M. tuberculosis. However, there is no information about the regulation of the synthesis of these lipids, which involves two different fatty acid synthase (FAS) systems. Our working hypothesis is that these two systems should be strictly co-regulated in order to maintain lipid homeostasis in this organism. We have characterized a transcriptional regulator that controls the expression of genes involved in FAS systems. This protein, whose structure appears to be unique within mycobacteria, is highly conserved in actinomycetes but lacks a close homolog in eukaryotes and in the host gut flora. We have identified a conserved 21 bp motif present in the promoter regions of these genes and demonstrated binding of purified protein to 300 bp DNA probes containing the motif. DNase I footprinting analysis verified that the protein under study protects the region containing the conserved sequence. Using M. smegmatis as a working model we found that this interaction modulates the expression of a number of FAS-related genes. This regulator, predicted to be a growth-essential gene in M. tuberculosis, is an attractive target for the development of new and specific antimycobacterial agents.