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分枝杆菌感染,包括结核病和麻风病,均属于世界范围的感染性疾病。由于治疗周期长,无法根除潜伏态细菌,以及多药耐药性结核分枝杆菌的检出率不断增加,给结核病的控制工作带来很大难度。目前,急需开发能有效控制该病的新药,包括可使耐药菌出现最小化的短期抗菌药物、可治疗多药耐药性结核病的新药以及可根除潜伏态结核分枝杆菌的药物。近年来,已发现了很多具有新化学结构的抗分枝杆菌的药物,其中有些展现出显著的抗敏感和耐药结核分枝杆菌的活性。特别是最近发现的二芳基喹啉具有绝佳的抗结核杆菌活性,此外,在对硝基咪唑吡喃类(nitroi midazopyrans)和噁唑烷酮类(oxazolidinones)的研究中也发现了令人鼓舞的结果。在明确了分枝杆菌基因组的前提下,对其的遗传学和生物化学研究使人们更加明确了分枝杆菌细胞壁的生物合成过程以及与其他病原菌不同的代谢途径,以致发现了许多可能的药物作用靶位。其中某些研究进展涉及到新的靶标酶或生化途径。本文对抗结核药物的开发进展进行综述,同时对那些现在临床上用来控制其他感染性疾病的药物在结核病治疗方面的应用加以讨论。此外,还就包括分枝杆菌细胞壁通透屏障在内的抗生素耐药机制和其他新的耐药机制进行讨论。
Mycobacterial infections, including tuberculosis and leprosy, are worldwide infectious diseases. Due to the long treatment period, the inability to eradicate latent bacteria and the increasing detection rate of multidrug-resistant Mycobacterium tuberculosis have brought great difficulty to the control of tuberculosis. At present, there is an urgent need to develop new drugs that can effectively control this disease, including short-term antimicrobial drugs that can minimize the emergence of drug-resistant bacteria, new drugs that can cure multi-drug resistant tuberculosis, and drugs that can eradicate latent M. tuberculosis. In recent years, many anti-mycobacterial drugs with new chemical structures have been found, some of which exhibit significant anti-allergic and drug-resistant Mycobacterium tuberculosis activity. In particular, the recently discovered diarylquinoline has excellent activity against Mycobacterium tuberculosis. In addition, it has also been found in studies of nitroi midazopyrans and oxazolidinones Inspirational result. With the clarification of the mycobacterial genome, the genetics and biochemistry of mycobacterial genome make it more clear that the mycobacterial cell wall biosynthesis process and the different metabolic pathways with other pathogens, so that many possible drug effects were found Target. Some of these advances involve new target enzymes or biochemical pathways. This article reviews the progress made in the development of anti-tuberculosis drugs and discusses the use of drugs that are currently clinically used to control other infectious diseases in the treatment of tuberculosis. In addition, antibiotic resistance mechanisms including the mycobacterial cell wall barrier and other new drug resistance mechanisms are discussed.