Multidrug resístanse pump AcrAB-TolC is required for hight-level TetA-mediated Tetracycline resístance in Escherichia coli

RICARDO DE CRISTÓBAL, PAULA VINCENT, RAÚL SALOMÓN.

Pinamar, Buenos Aires.

Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología molecular.; 2005

SAIB

Tetracycline (Tc) is an antibiotic which inhibits bacterial growth through the inhibition of protein synthesis. One mechanism of resistance among pathogenic strains is mediated by Tc efflux pumps which maintain its intracellular concentration at a low level. We observed that Escherichia coli tolC mutations severely reduced the high-level resistance to tetracycline afforded by Tn10– and plasmid–encoded TetA pumps. The reduction in the MIC was, in all cases, reverted by plasmid pAX629 carrying wild type tolC gene. The phenotype of Tc sensitivity was also seen with a Tc derivative, chlortetracycline (CTc). The influence of a tolC mutation on the expression of a tetA::lacZ gene fusion was examined. The expression of the fusion in the TolC– strain was similar to that in the TolC+ parent strain, suggesting that the effect of tolC mutations on Tc resistance was not due to a down-regulation of the tetA gene. A defect in Tc efflux in the tolC::Tn10 mutant was found by measuring the amount of TC accumulated. We demonstrated that mutational loss of the AcrAB multidrug efflux transporter had the same effect on the high-level resistance to Tc; therefore, it seems that tolC mutations act through inactivation of the AcrAB system These results are compatible with the hypothesis that the AcrAB pump is an important component in the development of high levels of resistance to Tc, perhaps by working in combination with TetA.