Keda Ying,Xinru Ren,Meiru Tong,Siyu Ye,Yuhong Shi,Qianjin Zhou,Jiong Chen
Multidrug-resistant (MDR) pathogens are a significant threat to aquaculture due to their resistance to most conventional drugs. AcrAB-TolC is a known MDR efflux pump that increases antibiotic resistance. Inhibiting such pumps is a promising strategy in drug discovery. In this study, phytocompounds derived from Commelina communis (Asiatic dayflower) have been identified as candidate inhibitors for AcrB of Aeromonas hydrophila through virtual screening, encompassing molecular docking and molecular dynamics (MD) simulation. Consequently, five phytocompounds from the Asiatic dayflower met the criteria as suggested by the TCMSP database. Among them, flavocommelin, luteolin, and delphin_qt, exhibiting values higher than or equal to the control PAβN, emerged as candidate inhibitors of AcrB protein according to molecular docking analysis. Luteolin, which adhered to Lipinski's rule of five, was stable in binding to AcrB in a 50 ns molecular dynamics simulation. Luteolin also attenuated the reduction in Nile Red fluorescence in a dose-dependent manner, indicating the actual inhibition of the AcrAB-TolC efflux pump of the MDR A. hydrophila Y-1. The checkerboard synergy analysis revealed that luteolin exerted a positive impact on the six tested antibiotics, with fractional inhibitory concentration (FIC) indexes ranging from 0.125 to 0.375. Luteolin and florfenicol were recognized for having the best synergistic activity. When Ctenopharyngodon idella (grass carp) and Plecoglossus altivelis (ayu) were infected by A. hydrophila Y-1, the combination of luteolin and florfenicol markedly enhanced the survival rate and declined the bacterial load, as compared to either luteolin or florfenicol alone. Thus, luteolin is an effective efflux pump inhibitor for AcrAB-TolC of A. hydrophila , enhancing antibiotic sensitivity and exhibiting synergistic effects with antibiotics.
Shuting Fang,Yiquan Huang,Zhangmin Xiang,Rong Zeng,Shulin Zeng,Shuqin Liu
The ever-increasing environmental risks posed by nanoplastics (NPs) have been drawing more concerns to their biological effects, but with limited information on pathogenic bacteria. This work reported the alterations in bacteriological properties of Escherichia coli O157:H7 (E. coli O157:H7) under exposure to polystyrene (PS) NPs of different sizes. Results found that E. coli O157:H7 growth was promoted by the addition of PS-NPs. At environmentally relevant exposure levels, E. coli O157:H7 underwent metabolic adaptation after different PS-NP treatments, showing differentiated responsive volatile metabolic features. Moreover, enzymatic activity analysis suggested that E. coli O157:H7 could address PS-NP-induced oxidative stress mainly via supporting glutathione (GSH) synthesis. Furthermore, it could fuel the TCA cycle through highly expressing regulatory enzymes as well with a greater response to small PS-NPs. Also, there was an observed increase in the expression of the AcrAB-TolC efflux pump after the treatment of PS below 100 nm and with a possible consequence of heightening E. coli O157:H7 resistance. Together, our findings provided the first look into the potential implications mediated by PS nanoparticles on E. coli O157:H7 growth and development and in turn emphasized a potential increased contamination of E. coli O157:H7 as a waterborne pathogen in PS-NP polluted water.
QiMing Tian,SiMin Wei,HongRui Su,ShuMei Zheng,ShuYa Xu,MingJiang Liu,RuoNan Bo,JinGui Li
The continuous emergence of multidrug-resistant (MDR) bacteria has posed an increasingly serious public health threat which urges people to develop some alternatives. Gallic acid (GA) is a natural ingredient in many traditional Chinese medicines , which has many biological activities, such as antibacterial, and antiseptic. Here, clinical isolates of MDR Escherichia coli ( E. coli ) were used to evaluate the antibacterial effect of GA and the underlying mechanism. The results revealed that GA exerted bactericidal activity and inhibited the formation of bacterial biofilm. GA enhanced the activities of ceftiofur sodium or tetracycline against E. coli , and facilitated antibiotic accumulation in bacteria. Further analysis of morphological alterations and efflux pump gene expressions confirmed that GA damaged outer and inner membranes, and suppressed the mRNA expressions of acrA, acrB, tolC, acrD and acrF involved in membrane permeability . In addition, GA showed protective effects against bacterial infection and improved the survival rates of Galleria mellonella and BALB/c mice. These data highlight a better understanding of GA against bacteria and provide an alternative strategy for MDR bacterial infection.
危险品化学品经营许可证（带存储）