Total alkaloids of sophorea alopecuroides-induced down-regulation of acrab-tolc efflux pump reverses susceptibility to ciprofloxacin in clinical multidrug resistant escherichia coli isolates

摘要

In this report, total alkaloids extracted from the seeds of Sophorea alopecuroides (TASA) was evaluated against clinical Escherichia coli isolates resistant to four tested antibiotics, ampicillin (AM), amikacin (AN), cefotaxime (CTX) and ciprofloxacin (CIP). The TASA showed an antibacterial activity against the multidrug resistant (MDR) isolates. In combination with TASA, synergistic effects on the tested antibiotics against the MRD isolates were observed. Similarly, the isolates pretreated with a lower dose of TASA yielded increased and stable susceptibilities to CIP by 16-32-fold determined by a microbroth dilution checkerboard method. Moreover, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed a constitutive overexpression of the AcrAB-TolC pump system in the tested MDR isolates. The pretreatment of MDR isolates with TASA resulted in a statistically down-regulated expression of acrA and acrB genes, and an up-regulated expression of acrR gene (p < 0.05). But the expression of tolC gene was not significantly altered (p > 0.05). These results suggested that the TASA-induced reversal resistance to CIP might be partially through a mechanism of inhibition of the AcrAB-TolC pump activity in these isolates, implying that the TASA can be used as a potential natural source to develop efflux pump inhibitors (EPI) against AcrAB-TolC pump mediated MDR in E. coli isolates.