多粘菌素菌种选育和发酵技术研究进展

Research Progress of Strain Breeding and Fermentation of Polymyxin

由于具有一定肾毒性和神经毒性,多粘菌素在过去相当长一段时间内一直是二线药物。耐药细菌的出现和相应疗药的有限使多粘菌素重新进入临床实践中,多粘菌素在治疗革兰阴性菌,特别是铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯杆菌导致的感染方面疗效确切,引起人们的极大重视。多粘菌素的发酵生产是其药理研究和临床应用的基础。然而,我国多粘菌素的发酵产量远低于发达国家,以致多粘菌素严重依赖进口且价格昂贵。本研究从多粘菌素菌种选育、培养基优化、培养条件优化和培养过程优化与控制等四个方面对近年来相关研究进行了梳理和总结,指出上述研究中用到的方法和策略,期望为多粘菌素工业生产和应用提供参考。

Polymyxin was a second-line drug in the past for a long period because it had a certain renal toxicity and neurotoxicity. It was returned to clinical practice due to the emergence of resistant bacteria and limited availability of effective drugs. In the treatment of infection caused by gram negative bacteria, especially Pseudomonas aeruginosa, Acinetobacter Bauman and Klebsiella pneumoniae, the curative effect of polymyxin was exact,which attracted people's great attention. The fermentation of polymyxin provided a foundation for its pharmacological research and clinical application. However, the fermentation yield of polymyxin in China was much less than developed countries, which lead to polymyxin in China was heavily dependent on imports and the price was very expensive. In this study, the strain breeding, medium optimization, culture conditions optimization, and culture process optimization and control of polymyxin have been reviewed and concluded in recent years. The methods and strategy used in the reports were proposed. Therefore, this study would provide valuable reference for the industrial production and application of polymyxin.