大肠杆菌、金黄色葡萄球菌对利福定耐药与包膜屏障改变的关系

选用金黄色葡萄球菌、大肠杆菌及变形杆菌敏感株,经药物梯度平皿筛选得到耐药性突变株,测定细菌生长浊度变化。以利福定(RFD)或EDTA分别作用时,耐药菌的生长曲线不受影响,RFD和EDTA合用,则耐药菌的生长曲线受到明显抑制。以~3H-RFD分别掺入敏感菌及耐药菌,前者的药物掺入量明显高于后者。电镜观察见耐药菌菌体变得粗短,表面粗糙,外膜增厚,膜皱折增多。以上结果提示,细菌包膜屏障在耐药性产生中具有重要作用。     

大肠杆菌,金黄色葡萄球菌对利福定耐药与包膜屏障改变的关系

The Rifamdine (RFD) resistant strains were obtained from wild types of S. aureus NCTC 6571, E. coli NCTC 10418 and Proteus vulgaris by drug concentration gradient plate. The experiment indicated that the growth inhibition of resistant cells induced by synergism of EDTA acting with RFD. Such results did not occur effectively if EDTA or RFD was added separately. The amount of 3H-RFD incorporated into cells of susceptible and resistant strains of E. coli and S. aureus was compared. The amount of 3H-RFD incorporated into susceptible cells was much greater than that of the resistant strains in E. coli cells. Ultrastructure comparison of sensitive and resistant cells showed that the surface of resistant cells was coarser and shorter, the outer membrane thickened and electron density increased. These results have shown that there is a close relationship between the resistance of bacteria induced by RFD and the decrease in the permeability of cell envelope barrier to the drug.     

细菌耐利福定与RNA多聚酶的关系

以药物梯度平皿筛选得到金黄色葡萄球菌NCTC6571、大肠杆菌NCTC10418及普通变形杆菌1065的耐利福定菌株。利福定能明显抑制~3H-尿苷掺入敏感菌株,而对耐药菌株的RNA合成无明显影响;利福定与利福平对标准RNA多聚酶活性的抑制随着药物剂量的增加而加强;提取及纯化RNA多聚酶,利福定能明显抑制敏感菌的酶活性,而对金黄色葡萄球菌NCTC6571与大肠杆菌NCTC10418耐药菌株的酶活性无明显影响。     

结核杆菌耐利福定与细菌RNA聚合酶变异关系的研究

选用结核杆菌H_(37)Rv,于体外诱导筛选获得耐利福定(1250μg/ml)菌株,检测了利福定抗结核杆菌活性及其与6种常用抗结核药物的交叉耐药性;以~3H-尿苷进行掺入实验,发现利福定明显抑制~3H-尿苷掺入敏感菌,而对掺入耐药菌则无抑制;提取及分析结核杆菌RNA聚合酶,发现敏感菌酶活性受利福定明显抑制,耐药菌酶活性则未见抑制。结果提示:结核杆菌耐利福定与耐药菌RNA聚合酶改变有关。     

利福定耐药机制探讨—耐药菌及敏感菌的形态学比较

本文报道利福定耐药及敏感细菌的形态学比较。扫描电镜见大肠杆菌耐药菌菌体变短,表面较敏感菌坚实、粗糙;透射电镜观察见耐药菌外膜增厚,电子密度增加。敏感菌以利福定(100μg/ml)处理4h后,光镜下可见菌体变得模糊,出现溶解现象;透射电镜见胞质疏松、核糖体减少并出现空泡。耐药菌经药物处理后无明显改变,但用药时加用EDTA,则出现与敏感菌类似的改变。该结果支持利福定耐药性与细菌包膜屏障改变有关。     

国产抗结核药物利福定耐药机理探讨——Ⅰ.细菌胞膜屏障对耐药性的影响

利福定(R761,Rifandin)是我国首先制成的抗结核、抗麻风病新药,并已广泛临床应用.化学名为异丁基哌嗪力复霉素SV.3(4-isobutyl-1-peperazinyl)Rifamycin SV化学结构与利福平相似.该药物具有抗菌效力强,口服吸收好,血清浓度高,用量较利福平少,毒付作用较利福平低等优点.由于临床用药量增加,而结核、麻风等疾病需长期用药,耐药性成为治疗中需要重视的问题.