title: AFM probing the mechanism of synergistic effects of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) with cefotaxime against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli.
abstract: BACKGROUND
  Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae poses serious challenges to clinicians because of its resistance to many classes of antibiotics.
  
  
  RESULTS
  The mechanism of synergistic activity of a combination of (-)-epigallocatechin-3-gallate (EGCG) and β-lactam antibiotics cefotaxime was studied on Extended-spectrum β-lactamase producing Escherichia coli (ESBL-EC), by visualizing the morphological alteration on the cell wall induced by the combination using atomic force microscopy (AFM). Cells at sub-MICs (sub-minimum inhibitory concentrations) of cefotaxime were initially filamentated but recovered to the normal shape later, whereas cells at sub-MICs of EGCG experienced temporal disturbance on the cell wall such as leakage and release of cellular debris and groove formation, but later recovered to the normal shape. In contrast, the combination of cefotaxime and EGCG at their respective sub-MICs induced permanent cellular damages as well as continuous elongation in cells and eventually killed them. Flow cytometry showed that intracellular oxidative stress levels in the cell treated with a combination of EGCG and cefotaxime at sub-MICs were higher than those in the cells treated with either cefotaxime or EGCG at sub-MICs.
  
  
  CONCLUSIONS
  These results suggest that the synergistic effect of EGCG between EGCG and cefotaxime against ESBL-EC is related to cooperative activity of exogenous and endogenous reactive oxygen species (ROS) generated by EGCG and cefotaxime, respectively.
authors.affiliation: Department of Chemistry and Nano Sciences, Ewha Womans University, Seoul, Korea.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Cui
authors.forename: So Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Hyunseok
authors.initials: H
authors.lastname: Kim
authors.forename: Jinki
authors.initials: J
authors.lastname: Yeom
authors.forename: Kisung
authors.initials: K
authors.lastname: Ko
authors.forename: Woojun
authors.initials: W
authors.lastname: Park
authors.forename: Sungsu
authors.initials: S
authors.lastname: Park
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002439:Cefotaxime / Q000494:pharmacology*; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D018625:Microscopy, Atomic Force; D018384:Oxidative Stress; D013662:Tea / Q000737:chemistry*; D013997:Time Factors; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D001618:beta-Lactamases; D002439:Cefotaxime