Total alkaloids of Sophora alopecuroides- and matrine-induced reactive oxygen species impair biofilm formation of Staphylococcus epidermidis and increase bacterial susceptibility to ciprofloxacin

Abstract

ObjectiveTo investigate the mechanism by which total alkaloids of Sophora alopecuroides (TASA) and matrine (MT) impair biofilm to increase the susceptibility of Staphylococcus epidermidis (S. epidermidis) to ciprofloxacin. MethodsThe minimum biofilm inhibitory concentration (mBIC) was determined using a 2-fold dilution method. Structure of biofilm of S. epidermidis was examined by Confocal Laser Scanning Microscope (CLSM). The cellular reactive oxygen species (ROS) was determined using a DCFH-DA assay. The key factors related to the regulation of ROS were accessed using respective kits. ResultsTASA and MT were more beneficial to impair biofilm of S. epidermidis than ciprofloxacin (CIP) (P < 0.05). TASA and MT were not easily developed resistance to biofilm-producing S. epidermidis. The mBIC of CIP decreased by 2–6-fold following the treatment of sub-biofilm inhibitory concentration (sub-BIC) TASA and MT, whereas the mBIC of CIP increased by 2-fold following a treatment of sub-BIC CIP from the first to sixth generations. TASA and MT can improve the production of ROS in biofilm-producing S. epidermidis. The ROS content was decreased 23%−33% following the treatment of sub-mBIC CIP, whereas ROS content increased 7%−24% following treatment with TASA + CIP and MT + CIP combination from the first to sixth generations. Nitric oxide (NO) as a ROS, which was consistent with the previously confirmed relationship between ROS and drug resistance. Related regulatory factors-superoxide dismutase (SOD) and glutathione peroxidase (GSH) could synergistically maintain the redox balance in vivo. ConclusionTASA and MT enhanced reactive oxygen species to restore the susceptibility of S. epidermidis to ciprofloxacin.