mtrR基因突变与淋病奈瑟菌多重耐药的相关性

Correlation between mtrR gene mutation and multi-drug resistant of Neisseria gonorrhoeae

目的了解临床分离的淋病奈瑟菌对常用抗菌药物的耐药性,探讨可传递多重耐药(mtr)系统mtrR基因突变与淋病奈瑟菌多重耐药的相关性。方法采用琼脂稀释法检测30株淋病奈瑟菌临床株对环丙沙星、青霉素、四环素、阿奇霉素、大观霉素和头孢曲松6种临床常用抗菌药物的最低抑菌浓度(MIC),同时采用纸片碘量法检测菌株是否产青霉素酶。选取其中仅对1种抗菌药物耐药的临床株和仅对2种抗菌药物同时耐药的临床株以及多重耐药淋病奈瑟菌株提取DNA,采用聚合酶链反应(PCR)扩增其mtrR基因,并将扩增产物测序,比较其与淋病奈瑟菌标准敏感株的差异。结果 30株淋病奈瑟菌中仅对1种抗菌药物耐药的有3株(10%),仅对2种抗菌药物同时耐药的有16株(53%),对3种抗菌药物同时耐药的有9株(30%),对4种药物同时耐药的有2株(7%)。30株淋病奈瑟菌的多重耐药率为37%。有7株菌(23%)检出青霉素酶阳性。仅对1种抗菌药物耐药和仅对2种抗菌药物同时耐药的临床株未发现mtrR基因突变;11株多重耐药临床株均有mtrR基因突变,有7株在第45位发生Gly(GGC→GAC)Asp突变,有4株在第51位发生Phe(TTC→GTC)Val突变。结论临床分离的淋病奈瑟菌多重耐药率较高,应持续监测淋病奈瑟菌的耐药性。mtrR基因的第45位Gly(GGC→GAC)Asp突变和第51位Phe(TTC→GTC)Val突变与淋病奈瑟菌的多重耐药密切相关。

Objective It is to study the drug resistance of Neisseria gonorrhoeae for common antibacterial agents, and to explore the correlation between mtrR system, mtrR gene mutation and multi-drug resistant of Neisseria gonorrhoeae.Methods Agar dilution method was used to detect the minimum bacteriostatic concentration （ MIC） of 30 strains of Neisseria gonorrhea clinical strains to 6 kinds of antimicrobial agents commonly used in clinic including ciprofloxacin, penicillin, tetracycline, az-ithromycin, spectinomycin and ceftriaxone, at the same time penicillin enzyme production was determined by paper iodine vol-ume method.The clinical strains with antimicrobial resistance for one kind of antimicrobial agents, the ones for two kinds and the ones with multi-drug resistance were selected and their DNA was extracted to detect mtrR gene by PCR method, and its differences with Neisseria gonorrhea standard sensitive strains were compared.Results There were 3 clinical strains （10%） with antimicrobial resistance for one kind of antimicrobial agents, 16 ones （53%） for two kinds and 9 ones （30%） for three kinds, 2 ones （7%） for 4 four kinds.The mulit-drug resistance rate was 37%.There were 7 strains whose penicillin enzyme was positive.Gene mutation of mtrR gene was not found in the strains with antimicrobial resistance for one and two kinds of antimicrobial agents, but all the strains with multi-drug resistance had gene mutation, in which 7 strains with Gly（ GGC-GAC） Asp mutation on the 45th position, 7 strains with Phe（ TTC-GTC） Val mutation on the 51th position.Conclusion Neisseria gonorrhoeae separated in clinic has a high multi-drug resistance rate, and their resistance should be continuously monitored.Gly（GGC-GAC） Asp mutation on the 45th position, Phe（TTC-GTC）Val mutation on the 51th position of mtrR gene are closely related with multi-drug resistance of Neisseria gonorrhoeae.