Abstract:

Objective　To explore the mutation characteristics of five genes (katG, mabA-inhA, oxyR-ahpC, kasA, and ndh) related to isoniazid resistance of Mycobacterium tuberculosis in clinical isolates in South China. Methods　A total of 380 clinical isolates of Mycobacterium tuberculosis from tuberculosis patients in South China which were sampled from the bio-bank of Mycobacteria in Guangzhou, including 236 isoniazid resistant strains and 144 isoniazid sensitive strains. The 5 isoniazid resistant gene fragments of 380 clinical isolates of Mycobacterium tuberculosis were sequenced and analyzed. Results　Twenty-nine gene mutation types at 26 sites in the isoniazid-resistant strains and 17 gene mutation types at 16 sites in the isoniazid-sensitive strains were found respectively. The most common mutations were 315AGC(S)→ACC(T) of katG and -15T→C of mabA-inhA, with the incidences of 48.73%(115/236), 17.37%(41/236), 9.72%(14/144), and 9.72%(14/144), respectively. Five mutations at 3 sites, 5 mutations at 5 sites, 13 mutations at 11 sites, 6 mutations at 6 sites, and 11 mutations at 11 sites were found in katG, mabA-inhA, oxyR-ahpC, kasA, and ndh, respectively. The incidences of five gene mutations in the isoniazid-resistant strains were 52.12%(123/236), 22.46%(53/236), 5.93%(14/236), 1.69%(4/236), and 2.54%(6/236) respectively, while those in the isoniazid-sensitive strains were 11.11%(16/144), 11.11%(16/144), 4.17%(6/144), 1.39%(2/144), and 3.47%(5/144), respectively. The incidences of no gene mutation, single gene mutation, and double gene mutations or more were 27.12% (64/236), 61.44% (145/236), and 11.44% (27/236) in the isoniazid-resistant strains and 76.39% (110/144), 21.53% (31/144), and 2.08% (3/144) in the isoniazid-sensitive strains. Conclusions　The gene mutation of isoniazid-resistant Mycobacterium tuberculosis in South China has its characteristics. It is essential to be studied further on the high gene mutation rate in isoniazid-sensitive strains.

Key words:

Mycobacterium tuberculosis, Drug susceptivity, Isoniazid, Drug resistant gene

摘要：

目的　探讨华南地区异烟肼耐药结核分枝杆菌临床分离株katG、mabA-inhA、oxyR-ahpC、kasA和ndh基因的突变特点。方法　在广州地区分枝杆菌菌株库中，选择异烟肼耐药性测定结果明确的380株来自华南地区结核病患者的结核分枝杆菌临床分离株，其中异烟肼耐药株236株和异烟肼敏感株144株，对380株结核分枝杆菌临床分离株的5种异烟肼耐药基因片段进行序列测定分析。描述性分析各基因突变出现的频率。结果　在INH耐药株和敏感株中分别发现26个位点29种突变类型、16个位点17种突变类型，均以katG基因315AGC（S）→ACC（T）、mabA-inhA基因-15T→C最为常见，发生率分别为48.73%（115/236）、17.37%（41/236）和9.72%（14/144）、9.72%（14/144）；在katG、mabA-inhA、oxyR-ahpC、kasA和ndh中分别发现3个位点5种突变、5个位点5种突变、11个位点13种突变、6个位点6种突变和11个位点11种突变，在INH耐药株和敏感株中5个基因突变的发生率分别为52.12%（123/236）、22.46%（53/236）、5.93%（14/236）、1.69%（4/236）、2.54%（6/236）和11.11%（16/144）、11.11%（16/144）、4.17%（6/144）、1.39%（2/144）、3.47%（5/144）；在INH耐药株和敏感株中无基因突变、单基因突变、双基因以上突变发生率分别为27.12%（64/236）、61.44%（145/236）、11.44%（27/236）和76.39%（110/144）、21.53%（31/144）、2.08%（3/144）。结论　华南地区异烟肼耐药结核分枝杆菌临床分离株耐药基因突变具有其特点，敏感株中基因突变发生率较高，值得进一步深入研究。

关键词:

结核分枝杆菌, 药物敏感性, 异烟肼, 耐药基因