MabR, a novel transcriptional regulator of mycolic acid biosynthesis in micobacteria.

SALZMAN, V; MONDINO, S; PEIRÚ, S; GAGO, G; GRAMAJO, H

Tucumán, Argentina

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Mycolic acids, the dominant feature of the Mycobacterium tuberculosis cell wall, are essential for the survival, virulence, and antibiotic exclusion of this human pathogen. Mycobacteria, unlike most bacteria, have two fatty acid synthases (FAS-I and FAS-II). Both of them are involved in the biosynthetic pathway of mycolic acids which regulation mechanism is still unknown. We discovered a new transcriptional regulator that controls the expression of fasII genes, named MabR. We found that MabR binds specifically to the fasII operon promoter region, pfasII. Moreover, DNAsaI footprinting analysis verified that the protein under study protects a highly conserved 21 bp motif in pfasII. Two 6 bp inverted repeats form part of this motif and are essential for the interaction of the regulator with the consensus sequence. Construction and further characterization of a mabR conditional mutant in M. smegmatis demonstrated that this regulator modulates the expression of fasII genes in vivo and confirmed that it is an essential component of the complex regulatory network involved in maintaining lipid homeostasis. Taking into account that MabR homologues are highly conserved in actinomycetes and are not present in eukaryotes or in the gut flora, it is tempting to speculate that MabR could be an attractive target for the development of new and specific antimycobacterial agents.