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: Silymarin and curcumin antimicrobial properties have been previously described against some infectious agents. The aims of the current study were the investigation of the antibacterial effects of these compounds on the expression of fimA, cdt, blaIMP1 and blaOXA-48 and AcrAB-TolC genes among multidrug-resistant Escherichia coli clinical isolates.: A total of five carbapenemase-producing E. coli strains were included. All of them carried blaIMP1 and blaOXA-48, ACR-AB, cdt, fimA and QepA genes. The antibiotic susceptibility test, imipenem, cefotaxime and ceftazidime minimum inhibitory concentration (MIC) and combine disk and Carba NP-test for carbapenemase production were performed. Silymarin and curcumin minimum inhibitory and bactericidal concentrations [MIC and minimum bactericidal concentration (MBC), respectively] were determined. The effect of 25 μg/ml concentration was also evaluated against gene expression. The quantitative real-time PCR was performed for the evaluation of genes expression.: Silymarin MIC and MBC were 256 and more than 256 μg/ml, respectively. Moreover, curcumin MIC and MBC concentrations were 128 and 256 μg/ml, respectively. Silymarin down-expressed the ACR-AB, cdt, fimA genes and QepA genes significantly (P < 0.05), but conferred no significant effect on blaIMP nor blaOXA-48 genes. Moreover, curcumin down-expressed the ACR-AB, QepA and blaIMP genes significantly (P < 0.05), but exhibited no significant effect against blaOXA-48, cdt and fimA genes.: In this study, curcumin and silymarin sub-MIC concentrations could significantly inhibit the expression of the ACR-AB, cdt, fimA, QepA and blaIMP genes at 25 μg/ml. Combating bacterial virulence is a proper strategy not only to inhibit the spread of infections, but also to prevent the appearance and spread of antibiotic nonsusceptible strains.