IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
ANALYSIS OF GENOMIC SEQUENCE OF TCH RESISTANT MUTANT FROM Mycobacterium tuberculosis
Autor/es:
BORTOLOTTI, A; SUAREZ, C; BELARDINELLI, JM; GORDON, S; MORBIDONI, HR
Reunión:
Congreso; XLVIII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2012
Resumen:
2-thiophen carboxylic acid hydrazide (TCH), used to differentiate between clinical isolates of and, exhibits high activity at the low microgram level only against these two pathogens. However, there is no information on its possible mechanisms of action. Our preliminary results showed that TCH does not inhibit mycolic acid synthesis, altthough it causes cell lysis and requires KatG, the catalaseperoxidase activator of the anti-tubercular drug Isoniazid. Aliquots of the reference strain H37Rv cultures were plated with different concentrations of TCH. In this way, we obtained 8 TCH resistant mutants and determinated their genomic sequence by Whole Genome Sequencing. Our bioinformatics analysis revealed a mutation in four of those mutants, located in the promoter region of C (alkylhydroperoxidereductase). This mutation was previously described in the literature only as associated with mutations in G. However, our mutants presented a wild-type sequence of this gene. The other four mutants displayed mutations in non essential genes (i.e. a putative malate synthase, a sensor of a two component system) or intergenic regions (upstream of the Rv3717 gene, involved in peptidoglycan recycling).We are currently constructing a merodiploid G strain to isolate TCH mutants in order to identify the molecular target for this drug.