Abstract：
In recent years, the evolution of antibiotic resistance has led to the inefficacy of several antibiotics, and the reverse of resistance was a novel method to solve this problem. We previously demonstrated that matrine (Mat) and berberine hydrochloride (Ber) had a synergistic effect against multidrug-resistant Escherichia coli (MDREC). This study aimed to demonstrate the effect of Mat combined with Ber in reversing the resistance of MDREC. The MDREC was sequenced passaged in the presence of Mat, Ber, and a combination of Mat and Ber, which did not affect its growth. The reverse rate was up to 39.67% after MDREC exposed to Mat + Ber for 15 days. The strain that reversed resistance was named drug resistance reversed E. coli (DRREC) and its resistance to ampicillin, streptomycin, gentamicin, and tetracycline was reversed. The MIC of Gentamicin Sulfate (GS) against DRREC decreased 128-fold to 0.63 µg/mL, and it was stable within 20 generations. Furthermore, the susceptible phenotype of DRREC remained stable within 20 generations, as well. The LD50 of DRREC for chickens was 8.69 × 109 CFU/mL. qRT-PCR assays revealed that the transcript levels of antibiotic-resistant genes and virulence genes in the DRREC strain were significantly lower than that in the MDREC strain (P < 0.05). In addition, GS decreased the death, decreased the bacterial loading in organs, alleviated the injury of the spleen and liver, and decreased the cytokine levels in the chickens infected by the DRREC strain. In contrast, the therapeutic effect of GS in chickens infected with MDREC was not as evident. These findings suggest that the combination of Mat and Ber has potential for reversing resistance to MDREC.
摘要：
近年来,抗生素耐药性的演变导致了几种抗生素的无效，而抗性逆转是解决这一问题的一种新方法。我们先前证明苦参碱（Mat）和盐酸小檗碱（Ber）对多重耐药大肠杆菌（MDREC）具有协同作用。本研究旨在证明Mat联合Ber逆转MDREC耐药性的作用。MDREC在Mat的存在下进行了传代测序，Ber,还有Mat和Ber的组合,这并不影响其增长。MDREC暴露于MatBer15天后，逆转率高达39.67％。逆转耐药性的菌株被命名为耐药逆转大肠杆菌(DRREC)及其对氨苄西林的耐药性,链霉素,庆大霉素,四环素逆转了.硫酸庆大霉素（GS）对DRREC的MIC下降128倍至0.63µg/mL，在20代内是稳定的。此外，DRREC的易感表型在20代内保持稳定，也是。DRREC对鸡的LD50为8.69×109CFU/mL。qRT-PCR检测结果显示，DRREC菌株中抗生素抗性基因和毒力基因的转录水平显著低于MDREC菌株（P<0.05）。此外,GS减少了死亡，减少了器官中的细菌负荷，减轻了脾脏和肝脏的损伤，并降低了被DRREC菌株感染的鸡中的细胞因子水平。相比之下,GS对感染MDREC的鸡的治疗效果不明显。这些发现表明Mat和Ber的组合具有逆转对MDREC的抗性的潜力。
