细菌AcrAB-TolC外排泵在幽门螺杆菌耐药中的作用及其机制

克服幽门螺杆菌（Hp）耐药，提高其根除率，是一世界性难题。外排泵是细菌耐药尤其是多重耐药产生的主要原因。研究表明抑制外排泵可逆转已发生的Hp耐药，但可否预防Hp耐药尚不明了。我们前期研究发现外排泵抑制剂，仅能提高少部分临床分离的天然多重耐药Hp对抗生素敏感性，与文献报道体外诱导的多重耐药Hp菌株外排泵抑制剂均可提高抗生素对其敏感的结果不致，外排泵在这两种Hp中的作用有何不同？为何不同？尚不清楚。此外，我们还发现中药草珊瑚可提高多重耐药Hp对抗生素敏感性，其是否通过抑制外排泵起作用有待确定。为此，本项目拟在前期工作的基础上，研究外排泵在天然多重耐药Hp中的作用，并观察外排泵抑制剂或敲除其相关基因可否逆转Hp的原发耐药和预防其继发耐药，并在此基础上观察中药草珊瑚等提高多重耐药Hp对抗生素的敏感性是否是通过抑制外排泵起作用。为外排泵抑制剂和中药作为外排泵抑制剂用于克服和预防Hp耐药提供依据。

It is a worldwide problem to overcome antibiotic resistance of Helicobacter pylori (H. pylori) and to improve the eradication rate of H. pylori. The efflux pump plays an important role in antibiotic resistance of H pylori, especially the multidrug resistance(MDR). Studies have indicated that efflux pump inhibitors (EPIs) could reverse the antibiotic resistance of H. pylori, but whether the EPIs could prevent the antibiotic resistance of H. pylori remains unclear. Our previous research found that EPIs could only increase the sensitivity to antibiotics of few clinical isolates of primary MDR of H. pylori, which is not agreed with some studies which indicated EPIs may all increase the sensitivity to antibiotics of MDR H. pylori by drug-induced ex vivo. What is the different effect of EPIs on those two kinds of H. pylori mentioned above and why does the different effect exist remain unclear. Our previous research also showed sarcandra glabra could increase the sensitivity to antibiotics of natural MDR H. pylori, but whether it could inhibit the efflux pump remains to be determined. Based on our previous research, the present study will evaluate the effect of efflux pump on clinical isolates of primary MDR H. pylori, and to observe whether the EPIs or the knockout of relative genes of efflux pump could reverse the primary antibiotic resistance of H. pylori and prevent the adaptive antibiotic resistance of H. pylori. We also want to investigate the effect of sarcandra glabra on the efflux pump. In a word, we perform this project in order to provide evidence for EPIs and Chinese medicine to reverse and prevent the antibiotic resistance of H. pylori in the clinic.