INVESTIGADORES
GRAMAJO Hugo Cesar
congresos y reuniones científicas
Título:
Characterization of a transcriptional regulator of mycolic acid biosynthesis in mycobacterium
Autor/es:
SALZMAN, V.; MONDINO, S.; GAGO, G. AND GRAMAJO, H
Lugar:
Huerta Grande-Cordoba
Reunión:
Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008
Institución organizadora:
SAIB
Resumen:
The most relevant lipids present in Mycobacterium cell envelope are
mycolic acids. These unusual fatty acids are essential for 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.
salzman@ibr.gov.ar