Total alkaloids from Sophora alopecuroides L. increase susceptibility of extended-spectrum β-lactamases producing Escherichia coli isolates to cefotaxime and ceftazidime
Total alkaloids from Sophora alopecuroides L. increase susceptibility of extended-spectrum β-lactamases producing Escherichia coli isolates to cefotaxime and ceftazidime
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DOI：
10.1007/s11655-011-0899-4
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发表时间：
2013-12
影响因子：
2.9
通讯作者：
Xuezhang Zhou;Fang Jia;Xiao-ming Liu;Cong Yang;Li Zhao;Yu-jiong Wang
中科院分区：
文献类型：
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作者：
Xuezhang Zhou;Fang Jia;Xiao-ming Liu;Cong Yang;Li Zhao;Yu-jiong Wang
目的评价苦豆子总生物碱的抑菌活性。 (TASA) 对临床分离的超广谱β-内酰胺酶 (ESBL) 产生大肠杆菌 (E. coli) 菌株。 方法 通过微肉汤稀释法和表型验证纸片扩散试验，研究 TASA 本身或与头孢噻肟 (CTX) 或头孢他啶 (CAZ) 组合的抗菌活性。 分离的产ESBLsE．粘菌菌株；通过评价分数抑菌浓度指数(FICI)来确定TASA与CTX或CAZ的相互作用。结果发现TASA本身或与CTX或CAZ组合具有抗菌活性。 TASA 对产 ESBL 分离株的最低抑菌浓度 (MIC) 为 12.5 mg/mL。在与亚抑制浓度的 TASA 组合中，观察到 CTX 和 CAZ 对产生 ESBL 的分离株具有协同作用。同样，通过微量稀释测定，暴露于较低剂量 TASA 的分离株对 CTX 和 CAZ 的敏感性增加了 8-16 倍。此外，ESBL 的酶检测表明，TASA 部分通过抑制这些分离株中 ESBL 活性的机制诱导对 CTX 和 CAZ 的逆转抗性。此外，在暴露于TASA后的测试分离株中，分子分析证实了这些分离株中编码ESBL基因的SHV型β-内酰胺酶，并且ESBL基因中没有引入突变。结论这些结果表明TASA可以用作具有逆转抗菌药物耐药性的药理活性的天然化合物的来源。这些发现还表明，TASA 与抗生素联合应用可能有助于控制和治疗由产 ESBL 肠杆菌科细菌引起的传染病。
ObjectiveTo evaluate the antimicrobial activity of total alkaloids extracted fromSophorea alopecuroidesL. (TASA) against clinical isolated extended-spectrum beta-lactamases (ESBLs) producingEscherichia coli(E. coli) strains.MethodsThe 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-producingE. colistrains; the interactions of TASA and CTX or CAZ were ascertained by evaluating the fractional inhibitory concentration index (FICI).ResultsThe 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.ConclusionsThese 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.