Regulation of mycolic acids biosynthesis in mycobacterium.

SALZMAN, VALENTINA; MONDINO, SONIA; GAGO, G; GRAMAJO, H

Biocell

Año: 2007 vol. 31 p. 66 - 66

0327-9545

The most relevant lipids present in Mycobacterium cell envelope are the 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. Microarrays and quantitative proteomics studies revealed that inhibition of M. tuberculosis mycolate production by isoniazid (INH) induces transcription of the FASII components present in the kas operon. We found an ORF (Rv2242) upstream the kas operon with homology to transcriptional regulators. This ORF is present in all the actinomycetes genomes analyzed. Therefore, our working hypothesis is that this ORF, proposed to be essential, codes for a transcriptional regulator of mycolic acid synthesis. Rv2242 was successfully expressed and purified by affinity chromatography. Purified protein binds specifically to a 300-base pair fragment containing the kas promoter. Moreover, DnasaI footprinting analysis revealed the presence of an inverted repeat in the DNA binding region that is conserved in all the actinomycetes kas promoters analyzed. This is the first report of the presence of a protein able to bind the kas operon promoter in vitro. We are currently studying the physiological role of this transcriptional regulator using M. smegmatis as a working model.