The Effects of Berberine in the Expression Quantities of Efflux Pump Genes hef'ABC of Helicobacter Pylori of Multi-drug resistance
Zhou Fan1, Xu Xiaoqing2, Peng Junwei3, Cao Qin2
1. Gastroenterology Department,The Third People’s Hospital of Huzhou,Huzhou,Zhejiang 313000,China; 2. Gastroenterology Department,Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China; 3. Department of integrated Chinese and Western medicine,Shanghai Minhang District Tumor Hospital,Shanghai 220240,China
AbstractObjective To study the the role of berberine(BBR) in the regulation of efflux pump genes hefABC in multi-drug resistant(MDR) strains of Helicobacter pylori(Hp). Methods ①Hp clinical isolates were tested the minimum inhibitory concentration for amoxicillin,levofloxacin,clarithromycin and metronidazole by E-test method.,in which sensitive strains and MDR strains were screened.②The expression quantities diffenrence of efflux pump genes hefABC between MDR group and sensitive group were detected by Real-time fluorescent quantitative polymerase chain reaction(RT-PCR).③The MIC values of berberine against MDR strains were determined by agar two-fold dilution method.After the MDR strains were cultured at 1/2 MIC concentration of berberine in liquid for 5 generations,RT-PCR was used to detect the mRNA expression difference of the efflux pump genes before and after the addition of berberine. Results ①A total of sixty Hp strains were isolated and screened including fifteen sensitive strains and twelve MDR strains.②The expression quantities of hefA、hefB in the MDR group are significantly higher than that in the sensitive group(P<0.05).There are no high expressions of hefC between two groups(P<0.05).③The expression quantities of Hp0605,Hp0606 of MDR group after the effects of berberine remarkably decrease,compared with that before treated with berberine,and the difference has statistical significance. Conclusions ①Multi-drug resistance of H.pylori is related to the high expression of efflux pump genes of Hp0605,Hp0606.②Berberine can inhibit drug resistance in some MDR strains by down-regulating the expression of efflux pump genes hefA and hefB.
Zhou Fan,Xu Xiaoqing,Peng Junwei, et al. The Effects of Berberine in the Expression Quantities of Efflux Pump Genes hef'ABC of Helicobacter Pylori of Multi-drug resistance[J]. journal1, 2024, 44(4): 1-4.
[1] MILLER A K,WILLIAMS S M.Helicobacter pylori infection causes both protective and deleterious effects in human health and disease[J].Gennes Immun,2021,22(4):218-226. [2] 刘文忠,谢勇,陆红,等.第五次全国幽门螺杆菌感染处理共识报告[J].胃肠病学,2017,22(06): 346-360. [3] MATSUMOTO H,SHIOTANI A,GRAHAMD Y.Current and future treatment of helicobacter pylori infection-s[J].Adv Exp Med Biol,2019,1149:211-225. [4] 侯宠,刘一品.幽门螺杆菌抗菌药物耐药分子机制的研究进展[J].胃肠病学,2021,26(03): 171-175. [5] Du D,Wang-Kan X,Neuberger A,et al.Multidrug efflux pumps:Structure,function and regulation[J].Nature Re views Microbiology,2018,16(9):523-539. [6] BACHIR M,ALLEMR,BENEJAT L,et al.Molecular detection of mutations involved inHelicobacter pyloriantibiotic resistance in Algeria[J].J Antimicrob Chemother,2018,73(8) :2034-2038. [7] BEHESHTIROUY S,EYVAZI S,TARHRIZ V.Evaluation of mutations in 23S rRNA,rdxA and frxA genes of Helicobacter pylori in paraffin-embedded gastricbiopsy specimens from Iranian gastric cancer and gastritis patients[J].J Gastrointest Cancer,2021,52(1):207-211. [8] Thai KM,Ngo TD,Phan TV,et al.Virtual screening for novel Staphylococcus Aureus NorA efflux pump inhibitors from natural products[J].Med Chem,2015,11(2):135-155. [9] Chetri S,Bhowmik D,Paul D,et al.AcrAB-TolC efflux pump system plays a role in carbapenem non-susc -eptibility in Escherichiacoli[J].BMC Microbiol,2019,19(1):210. [10] 童静,李昌平.外排泵系统与幽门螺杆菌抗生素耐药性的研究进展[J].现代临床医学,2022,48(06):461-464. [11] 王琼,吴芳草,郭长城,等.以Real-time PCR方法检测耐药幽门螺杆菌中hefABC基因的表达[J].基因组学与应用生物学,2019,38(04):1797-1803. [12] 赵晶,戴金峰,黄宣,等.幽门螺杆菌耐药性及其与外排泵基因hefABC相关性[J].中华医院感染学杂志,2020,30(21):3233-3237. [13] 陈元旺. 细菌AcrAB-TolC外排泵在幽门螺杆菌耐药中的作用及机制[D].南昌:南昌大学,2014. [14] 张石磊,翟向和,王春光,等.应用高通量实时荧光定量PCR方法检测小檗碱对多药耐药大肠杆菌耐药基因的影响[J].中国兽医学报,2020,40(09):1737-1745. [15] 刘三侠. 小檗碱提取物抑制多重耐药大肠埃希菌外排喹诺酮类药物的研究[D].重庆:西南大学,2013. [16] 顾觉奋. 外排泵抑制剂研究进展[J].国外医药(抗生素分册),2020,41(01):1-10.