title: Total alkaloids from Sophora alopecuroides L. increase susceptibility of extended-spectrum β-lactamases producing Escherichia coli isolates to cefotaxime and ceftazidime.
abstract: OBJECTIVE
  To evaluate the antimicrobial activity of total alkaloids extracted from Sophorea alopecuroides L. (TASA) against clinical isolated extended-spectrum beta-lactamases (ESBLs) producing Escherichia coli (E. coli) strains.
  
  
  METHODS
  The antibacterial activity of TASA either itself or in combination with cefotaxime (CTX) or ceftazidime (CAZ) was investigated by using the microbroth dilution method and phenotypic confirmatory disk diffusion test against three clinical isolated ESBLs-producing E. coli strains; the interactions of TASA and CTX or CAZ were ascertained by evaluating the fractional inhibitory concentration index (FICI).
  
  
  RESULTS
  The antibacterial activity of either TASA itself or in combination with CTX or CAZ was found. The minimum inhibitory concentration (MICs) of TASA against the ESBLs producing isolates was 12.5 mg/mL. In the combinations with a sub-inhibitory concentration of TASA, a synergistic effect on CTX and CAZ against the ESBLs producing isolates was observed. Similarly, the isolates exposed to lower dose of TASA yielded an increased susceptibility to CTX and CAZ by 8-16 folds determined by microdilution assay. Moreover, enzymatic detection of ESBLs demonstrated that TASA induced reversal resistance to CTX and CAZ partially by a mechanism of inhibition of ESBLs activity in these isolates. Additionally, in the tested isolates following the exposure of TASA, molecular analysis verified the SHV-type beta-lactamase encoding ESBL gene in these isolates, and no mutation was introduced into the ESBL gene.
  
  
  CONCLUSIONS
  These results suggest that TASA could be used as a source of natural compound with pharmacological activity of reversal resistance to antimicrobial agent. These findings also indicated that the application of the TASA in combination with antibiotics might prove useful in the control and treatment of infectious diseases caused by the ESBLs producing enterobacteriaceae.
authors.affiliation: Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, College of Life Science, Ningxia University, Yinchuan, 750021, China.
authors.forename: Xue-zhang
authors.initials: XZ
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Jia
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Liu
authors.forename: Cong
authors.initials: C
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Yu-jiong
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D002439:Cefotaxime / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D017931:DNA Primers; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D029909:Sophora / Q000737:chemistry*; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D017931:DNA Primers; D002442:Ceftazidime; D001618:beta-Lactamases; D002439:Cefotaxime