结核分枝杆菌对异烟肼耐药的分子机制研究进展

The progresses of molecular mechanism of Isoniazid resistance in Mycobacterium Tuberculosis

结核病是由结核分枝杆菌引起的一种威胁全球健康的传染性疾病。异烟肼是结核病治疗应用最广泛的药物之一。前体异烟肼通过过氧化氢-过氧化物酶(Kat G)激活,活化的异烟肼可抑制靶蛋白Inh A。异烟肼耐药的分子机制涉及多个基因,其中kat G基因突变是异烟肼耐药主要的原因,另外还有inh A、kas A、oxyR基因等。外排泵系统在异烟肼耐药方面也起着重要作用。了解异烟肼抗结核分枝杆菌作用机制及结核分枝杆菌耐异烟肼的分子机制将有助于异烟肼耐药结核病的诊治。

Mycobacterium tuberculosis is the causative agent of tuberculosis,which is a threat to public health worldwide.Isoniazid is one of the most active compounds used to treat tuberculosis worldwide.The pro-drug isoniazid is activated by catalase-peroxidase(KatG),and the active isoniazid products are targeted to InhA.The molecular mechanisms of isoniazid resistance involve several genes mutations.Mutation in the katG gene is the major cause for isoniazid resistance,followed by inhA,kasA,oxyR.Efflux pump systems also play important role in conferring isoniazid resistance.Understanding the mechanisms operating behind isoniazid action and resistance would enable better diagnosis and treatment of isoniazid-resistant tuberculosis.