上海交通大学学报（医学版）

›› 2011, Vol. 31 ›› Issue (11): 1583-.doi: 10.3969/j.issn.1674-8115.2011.11.017

• 论著（临床研究） • 上一篇    下一篇

武汉地区结核分枝杆菌氨基糖苷类抗生素耐药分离株rpsL和rrs基因特征分析

温子禄1,2, 沈建国3, 张朝宝1, 余晓丽1, 陈 平1, 唐神结4, 郭晓奎2, 张舒林2   

  1. 1.武汉工业学院生物与制药工程学院, 武汉 430023； 2.上海交通大学 |基础医学院病原生物学教研室, 上海 200025； 3.南阳理工学院, 南阳 473004； 4.同济大学附属上海市肺科医院结核科, 上海 200433
  • 出版日期:2011-11-28 发布日期:2011-11-29
  • 通讯作者: 余晓丽, 电子信箱: yxll268@126.com；张舒林, 电子信箱: shulinzhang@sjtu.edu.cn。
  • 作者简介:温子禄（1985—）, 女, 硕士生；电子信箱: wenzilu1985@163.com。
  • 基金资助:

    “十一五”国家科技重大专项基金（2009ZX10003-017和2009ZX10004-313）和武汉工业学院2010年研究生创新基金项目（2010cx016）

Characterization of |rpsL and rrs genes of aminoglycoside-resistant clinical isolates of Mycobacterium tuberculosis in Wuhan

WEN Zi-lu1,2, SHEN Jian-guo3, ZHANG Chao-bao1, YU Xiao-li1, CHEN Ping1, TANG Shen-jie4, GUO Xiao-kui2, ZHANG Shu-lin2   

  1. 1.School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China；2.Department of Medical Microbiology and Parasitology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China；3.Nanyang Institute of Technology, Nanyang 473004, China；4.Department of |Tuberculosis, the Pulmonary Hospital Affiliated to Tongji University, Shanghai 200433, China
  • Online:2011-11-28 Published:2011-11-29
  • Supported by:

    National Key Technology Program in the 11th Five-Year Plan of China, 2009ZX10003-017, 2009ZX10004-313；Graduate Innovation Foundation of Wuhan Polytechnic University in 2010, 2010cx016

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摘要：

目的 阐明武汉地区结核分枝杆菌分离株氨基糖苷类药物耐药相关基因rpsL和rrs的分子突变特征。方法 从武汉医疗救治中心共收集69株结核分枝杆菌的临床菌株，包括耐链霉素（SM）菌株35株（其中4株同时对卡那霉素耐药）和SM敏感菌株34株（其中全敏感20株）。采用PCR直接测序法分析rpsL和rrs基因的分子突变特征。结果 35株SM耐药株中有26株（74.3%）检测到rpsL突变，突变位点集中在第43位和第88位密码子，并发现了1个新的突变类型Lys88Glu；13株耐药株（37.1%）检测到四种不同类型的rrs基因突变，分别为A1401G（17.1%，6/35）、A514C（14.3%，5/35）、G1487A（2.9%，1/35）和C517T（2.9%，1/35），1株全敏感菌株的rrs基因发生了C1029T突变。卡那霉素耐药株中只有3株检测到了rrs突变，并发现了一种rrs基因尚未见报道的G1487A突变类型。结论 结核分枝杆菌对氨基糖苷类药物的耐药与rpsL和rrs突变相关，耐药基因突变类型存在地域差异。

关键词: 结核分枝杆菌, 氨基糖苷类, 耐药, rpsL基因, rrs基因

Abstract:

Objective To characterize the rpsL and rrs genes of aminoglycoside-resistant clinical isolates of Mycobacterium tuberculosis in Wuhan. Methods Sixty-nine clinical isolates of Mycobacterium tuberculosis were collected from Wuhan Medical Treatment Center, including 35 streptomycin (SM)resistance isolates (4 were also resistant to kanamycin) and 34  isolates susceptible to SM (20 were pan-susceptible). Mutation characteristics of rpsL and rrs genes were analyzed with PCR direct sequencing. Results Of the 35 SM-resistant clinical isolates, 26 (74.3%) carried mutations in rpsL gene, with rpsL Lys43Arg and Lys88Arg being the most common rpsL mutations, and one new mutation in codon 88 of rpsL (Lys88Glu) was detected. Four types of mutations in rrs gene in 13 resistant isolates (37.1%) including A1401G (17.1%, 6/35), A514C (14.2%, 5/35), G1487A (2.9%, 1/35) and C517T (2.9%, 1/35) were revealed, and one pan-susceptible  isolate presenting C1029T mutation in rrs gene was detected. The mutations in rrs gene were only found in 3 kanamycin-resistant isolates, and G1487A mutation was detected in rrs gene, which was first reported. Conclusion Aminoglycoside-resistance of Mycobacterium tuberculosis is related to rpsL and rrs gene mutations, and the characteristics of these genes are diverse due to geographical differences.

Key words: Mycobacterium tuberculosis, aminoglycoside, drug resistance, rpsL gene, rrs gene