| 结核分枝杆菌环丝氨酸药物敏感性及耐药机制研究 |
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| 引用本文： | 牛金霞,崔振玲,逄文慧,朱长太,范琳. 结核分枝杆菌环丝氨酸药物敏感性及耐药机制研究[J]. 中国人兽共患病杂志, 2019, 35(1): 39-44. DOI: 10.3969/j.issn.1002-2694.2018.00.217 |
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| 作者姓名： | 牛金霞 崔振玲 逄文慧 朱长太 范琳 |
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| 作者单位： | 1. 上海海洋大学水产与生命学院,上海 201306; 2. 上海交通大学附属第六人民医院输血科,上海 200233; 3. 同济大学附属上海市肺科医院,结核病临床研究中心,上海市结核病(肺)重点实验室,上海 200433; 4. 中国海洋大学环境科学与工程学院,青岛 266100 |
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| 基金项目： | 上海市科委资助课题(No.14411966500) |
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| 摘 要： | 目的检测耐多药结核病(MDR-TB)临床分离株的环丝氨酸最低抑菌浓度(MIC),并从基因水平进行环丝氨酸耐药机制的研究,为环丝氨酸的快速耐药测定提供理论依据。方法采用Middlebrook 7H9液体培养基,在96孔板中对140株MDR-TB和37株敏感结核分枝杆菌(MTB)临床分离株进行环丝氨酸药敏试验,筛选出对环丝氨酸耐药及敏感的菌株,再对Ald、Alr、ddlA基因进行突变位点及基因表达量的分析。结果 MDR-TB对环丝氨酸的耐药率仅为4.28%,初步将MIC≥32μg/mL的结核分枝杆菌菌株判定为对环丝氨酸耐药;Ald、Alr、ddlA基因位点突变与结核分枝杆菌对环丝氨酸耐药无明显相关性,环丝氨酸耐药菌株在Alr基因位点处基因表达量明显高于敏感菌株。结论目前临床的MDR-TB患者对环丝氨酸的耐药率较低,使用环丝氨酸治疗MDR-TB是一种有效的选择。尚未发现明确的环丝氨酸耐药突变位点,但Alr基因的过表达与MTB环丝氨酸耐药高度相关,可能是其耐药的新机制。
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| 关 键 词： | 环丝氨酸 药敏试验 耐多药结核分枝杆菌 广泛耐药结核分枝杆菌 耐药机制 |
| 收稿时间： | 2018-02-22 |
Mycobacterium tuberculosis drug susceptibility and drug resistance mechanism to cycloserine |
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| NIU Jin-xia,CUI Zhen-ling,PANG Wen-hui,ZHU Chang-tai,FAN Lin. Mycobacterium tuberculosis drug susceptibility and drug resistance mechanism to cycloserine[J]. Chinese Journal of Zoonoses, 2019, 35(1): 39-44. DOI: 10.3969/j.issn.1002-2694.2018.00.217 |
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| Authors: | NIU Jin-xia CUI Zhen-ling PANG Wen-hui ZHU Chang-tai FAN Lin |
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| Affiliation: | 1. Shanghai Ocean University, College of Fisheries and Life Sciences, Shanghai 201306, China; 2. Department of Transfusion, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China; 3. Shanghai Pulmonary Hospital, Tongji University School of Medicine,Shanghai Key Laboratory of Tuberculosis Shanghai 200433, China; 4. China Ocean University, College of Environmental Science and Engineering, Qingdao 266100, China |
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| Abstract: | To detect the minimum inhibitory concentration of (MIC) circulating serine in clinical isolates of multidrug-resistant tuberculosis (MDR-TB), we studied the resistance mechanism of the genotypes of cycloserine-resistance Mycobacterium tuberculosis (M. tuberculosis), and provide the scientific evidence for the rapid resistance determination of cycloserine. The 140 clinical strains of drug-resistant M. tuberculosis and 37 clinical strains of drug-susceptible M. tuberculosis were isolated and tested by Middlebrook 7H9 liquid medium in 96-well plate. The Ald, Alr and ddlA mutations and gene expression levels were analysed to define the mechanism of cycloserine-resistant M. tuberculosis. The results showed cycloserine-resistance rates were as low as 4.28% in 140 strains of drug-resistant M. tuberculosis, we preliminarily defined the MICs of M. tuberculosis ≥32 μg/mL as cycloserine-resistance. There were no significant correlations between Ald, Alr, ddlA gene mutations and cycloserine-resistant M. tuberculosis. The Alr gene expression levels in cycloserine-resistant M. tuberculosis were significantly higher than those in cycloserine-susceptible M. tuberculosis. It is indicated that the drug resistance rate of cycloserine is low in MDR-TB, suggesting that cycloserine can be an effective and reliable clinical choice for treatment on MDR-TB. The cycloserine-resistance mutation in MTB has not been found, yet the overexpression of Alr gene found to be highly related to the cycloserine-resistance of MTB, providing a possible explanation of MTB resistance mechanism. |
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| Keywords: | cycloserine drug sensitivity testing MDR-MTB XDR-MTB drug-resistant mechanism |
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