Antibiotic resistance mechanisms in M. tuberculosis: an update.
Antibiotic resistance mechanisms in M. tuberculosis: an update.
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DOI：
10.1007/s00204-016-1727-6
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发表时间：
2016-07
影响因子：
6.1
通讯作者：
Nguyen L
中科院分区：
文献类型：
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作者：
Nguyen L
结核病（TB）的治疗一直是一个治疗挑战，不仅因为结核分枝杆菌对抗生素具有天然的高耐药性，而且还因为新获得的突变赋予了进一步的耐药性。目前的标准化治疗方案要求患者在医护人员的直接观察下每天服用最多四种药物，持续 6-9 个月。尽管它们在治疗药物敏感结核病方面相当有效，但这些漫长的治疗常常导致患者不依从治疗，从而促进结核分枝杆菌菌株的出现，这些菌株对少数可用的抗结核药物越来越耐药。结核分枝杆菌的快速演变，从单一耐药菌株到多重耐药菌株、广泛耐药菌株和最近的完全耐药菌株，如果不尽快推出新的治疗选择，结核病将有可能再次成为无法治疗的疾病。在这里，我讨论结核分枝杆菌对抗生素产生深刻耐药性的分子机制。这些知识可能有助于制定削弱耐药性的新策略，从而增强现有抗生素针对药物敏感和耐药结核分枝杆菌菌株的效力。
Treatment of tuberculosis (TB) has been a therapeutic challenge because of not only the naturally high resistance level of Mycobacterium tuberculosis to antibiotics but also the newly acquired mutations that confer further resistance. Currently standardized regimens require patients to daily ingest up to four drugs under direct observation of a healthcare worker for a period of 6–9 months. Although they are quite effective in treating drug susceptible TB, these lengthy treatments often lead to patient non-adherence, which catalyzes for the emergence of M. tuberculosis strains that are increasingly resistant to the few available anti-TB drugs. The rapid evolution of M. tuberculosis, from mono-drug-resistant to multiple drug-resistant, extensively drug-resistant and most recently totally drug-resistant strains, is threatening to make TB once again an untreatable disease if new therapeutic options do not soon become available. Here, I discuss the molecular mechanisms by which M. tuberculosis confers its profound resistance to antibiotics. This knowledge may help in developing novel strategies for weakening drug resistance, thus enhancing the potency of available antibiotics against both drug susceptible and resistant M. tuberculosis strains.