Inhibitory effects of silybin on the efflux pump of methicillin-resistant Staphylococcus aureus

Bacterial multidrug resistance efflux systems serve an important role in antimicrobial resistance. Thus, identifying novel and effective efflux pump inhibitors that are safe with no adverse side effects is urgently required. Silybin is a flavonolignan component of the extract from the milk thistle seed. To order to investigate the mechanism by which silybin inhibits the efflux system of methicillin-resistant Staphylococcus aureus (MRSA), antimicrobial susceptibility testing and the double-plate method were used to evaluate the effect of silybin on MRSA41577. The ability of silybin to inhibit the efflux of ciprofloxacin from MRSA was evaluated by performing a fluorescence assay. Reverse transcription-quantitative polymerase chain reaction analysis revealed that silybin reduced the expression of the quinolone resistance protein NorA (norA) and quaternary ammonium resistance proteins A/B (qacA/B) efflux genes in MRSA. This suggested that silybin may effectively inhibit the efflux system of MRSA41577. Compared with the control, MRSA41577 treated with silybin for 16 h exhibited a 36 and 49% reduction in the expression of norA and qacA/B, respectively. Inhibition of the expression of these genes by silybin restored the sensitivity of MRSA41577 to antibiotics, indicating that efflux pump inhibitors, which act by inhibiting the efflux system of MRSA, may disrupt the MRSA resistance to antibiotics, rendering the bacteria sensitive to these drugs.