IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Suppression of amikacin resistance due to aac(6’)-Ib by RNase P-based antisense technology
Autor/es:
SOLER BISTUE, A J C; HA, H; ZORREGUIETA, A; TOLMASKY, M E
Lugar:
Centro Cultural Parque de España - Rosario, Argentina.
Reunión:
Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2006
Institución organizadora:
SAIB
Resumen:
Antimicrobial resistance is a growing concern especially in third world countries.  Aminoglycoside 6’-N-acetyltransferases are a group of enzymes that catalyze the transfer of an acetyl group from acetyl coenzyme A to a primary amine in a wide variety of acceptor molecules including clinically important aminoglycosides (Ag). Among them, AAC(6’)-Ib is commonly found in the clinical environment and catalyzes the inactivation of amikacin and other important Ag. The aim of our study was to silence the gene coding for this enzyme using an RNase P-based antisense strategy. Five antisense oligoribonucleotides (ORNs) were designed to target single stranded regions of the mRNA. All five efficiently mediated in vitro RNase P degradation of aac(6’)-Ib mRNA. Selected ORNs were then cloned under T7 promoter control. The recombinant plasmids were introduced into Eschericha coli BL-21(DE3) already harboring a compatible low copy number plasmid carrying aac(6’)-Ib. Growth curves showed that the three strains were inhibited by of 15ug/ml of amikacin. These results suggest that antisense technology based on RNAse P can be a viable strategy to deal with the growing problem of resistance to amikacin.