Tannic Acid as a Potential Modulator of Norfloxacin Resistance in Staphylococcus Aureus Overexpressing norA

Abstract

Background: Tannins have shown inhibitory effects against pathogenic bacteria, and these properties make tannins potential modifying agents in bacterial resistance. Methods: The minimum inhibitory concentration (MIC) of tannic acid (TA), gallic acid (GA) and norfloxacin (Nor) against Staphylococcus aureus SA-1119 (NorA-effluxing strain) was determined using broth microdilution tests. To assess the modulation of antibiotic resistance, the MIC of Nor was determined in growth media with or without TA or GA at a subinhibitory concentration (1/4 MIC). The checkerboard method was performed to obtain the fractional inhibitory concentration index (FICI) for the combined application of TA and Nor. Results: TA displayed a weak inhibitory effect (MIC 512 μg/ml) against S. aureus SA-1119, while no inhibitory effect was displayed by GA (MIC >512 μg/ml). However, when TA was tested at a subinhibitory concentration in combination with Nor, the MIC of Nor against S. aureus SA-1119 decreased from 128 to 4 μg/ml (32-fold); this effect was not observed for GA. In the checkerboard assay, the MIC of TA and Nor decreased from 512 to 128 μg/ml (4-fold) and from 128 to 8 μg/ml (16-fold), respectively. The combination of TA and Nor presented an FICI as low as 0.31, which indicates a synergistic interaction. Conclusions: TA is a potential agent for increasing the clinical efficacy of Nor to control resistant S. aureus.