鼠伤寒沙门氏菌对三甲氧苄二氨嘧啶耐药机制的研究

STUDIES ON THE MECHANISMS OF RESISTANCE TO TRIMETHOPRIM IN SALMONELLA TYPHIMURIUM

对临床分离的鼠伤寒沙门氏菌进行了三甲氧苄二氨嘧啶(TMP)耐药机制的研究。结果表明,50株鼠伤寒沙门氏菌对 TMP 的耐药率为76%,其中7株菌对 TMP 高度耐药。7株耐药菌中有4株含有不同的质粒,TMP 耐药质粒可以在种内和种间转移,而且8%的 SDS 可以有效地消除 R 质粒。比较不同 TMP 耐药菌和对照菌的二氧叶酸还原酶(DHFR)活力和特性得出,鼠伤寒沙门氏菌 TMP 耐药机制为:无质粒菌的 TMP 耐药是由于染色体编码的 DHFR过量产生所致,TMP 对该酶的产生起诱导作用.含质粒菌是由于 R 质粒编码产生了 Ia 型抗TMP 的 DHFR 和 R 质粒编码产生了另一种新型的抗 TMP 的 DHFR,后者目前尚无报道。此研究结果为临床合理用药及控制致病菌的耐药性发展和传播提供了理论依据。

The mechanisms of resistance to trimethoprim(TMP)in the clinical isolates of Salmonellatyphimurium were studied.The experimental results indicated that the frequency of TMPresistance of 50 strains of Salmonella typhimurium was 76%.Seven of the resistant strainswere highly resistant to TMP and four of them contained different plasmids which couldtransfer in the same species and between different ones,and could be eliminated with 8% ofSDS.The results of comparing the activities and characteristics of dihydrofolate reductase(DHFR)in crude extracts from seven resistant strains and those from controls suggestedthat overproduction of the chromosomal DHFR was the resistance mechanisms in threeplasmid-free strains and the levels of DHFR activity of the strains was increased duringprolonged exposure to TMP in vitro.However resistance to TMP of the plasmid-containingstrains resulted from production of plasmid-mediated TMP resistant type Ia DHFR and anew type DHFR which has not been reported up to now.The pres work provided thetheoretical basis for clinical use of TMP and attempts to suppress development and spreadof duge resistance of pathogenic bacteria.