Combination of anti-tuberculosis drugs with pomegranate juice against multidrug- resistant tb and examination of the influence of this mix on resistant and efflux pump genes

The aim of present study was to investigate the effect of fresh pomegranate juice (FPJ) on the antibacterial activity of anti-tuberculosis drugs (Rifampin (R) and Isoniazid (INH)) against MDR-TB clinical isolates. Four concentrations of fresh pomegranate juice (FPJ) (5%, 10%, 15%, and 20%) were evaluated in combination with R and INH at a dose range of (1.0 µg/ml), and (0.1µg/ml), respectively. Moreover, this study investigated individual phenolic compounds of FPJ by using highperformance liquid chromatography (HPLC). The total polyphenols (TP), total flavonoid (TF), total anthocyanins content (TAC), and the antioxidant capacity were also assessed in FPJ. Additionally,we evaluated the contribution of resistant genes associated with INH and R resistance plus six putative drug efflux pump genes to the drug resistance levels in MDR-TB clinical isolates. While the expression level of katG was down-regulated in 24/27 (88.88%) MDR-TB isolates, inhA, oxyR-ahpC, and rpoB appeared to be either overexpressed or up-regulated in 8/ 27 (29.62%), 4/27 (14.81 %), and 24/ 27 (88.88%), respectively in MDR-TB isolates. Moreover, the efflux pump genes drrA, drrB, efpA