工业微生物的噬菌体感染与防治策略

Strategies to prevent bacteriophage infection in industrial fermentation

摘要:

以细菌为基础的生物技术在蓬勃发展的同时也不断受到噬菌体感染的威胁，噬菌体感染已成为微生物发酵过程中的一个顽疾，其实质是噬菌体与细菌之间复杂的共进化关系。在漫长的进化过程中，噬菌体已经形成了多种针对细菌抗性系统的逃逸机制。合理的工厂设计、菌株的轮换策略和传统的基因工程方法能在一定程度上降低噬菌体感染的风险，但仍然无法避免。基于CRISPR-Cas系统的防治策略仅需噬菌体的序列信息就可以理性设计噬菌体抗性菌株，且可以通过叠加效应不断增强菌种抗性，从而避免噬菌体的逃逸；群体感应信号分子则可以从整体水平上调节细菌的噬菌体抗性。这些新发现为噬菌体感染问题的解决带了新的希望，而噬菌体基因组编辑技术和合成生物学的快速发展则将进一步加深人们对噬菌体感染防治领域的认识。

Abstract:

During the development of bacteria-based biotechnology, bacteriophage infection is one of the constant threats and troublesome problems in industrial fermentation. The core of puzzled bacteriophage infection is a complex arm race of coevolution between bacteriophages and their hosts where bacteriophage has evolved lots of escaped ways against bacterial resistance mechanisms. The strategies of rationally designing factories and rotation of starter strains could reduce the risk of bacteriophage infection, but often fail to avoid. Genetic engineering to increase bacterial resistance is one of the strategies to prevent bacteriophage infection and more knowledge about bacteriophage and its host is needed. Recently, there are some new findings on bacterial resistance mechanisms which provide new solutions for bacteriophage infection. For example, it is possible for a rational design of resistant strains to use CRISPR-Cas based technologies just based on the sequences of bacteriophages. Moreover, it is also possible to avoid the escape of bacteriophage by iteratively building up resistance levels to generate robust industrial starter cultures. Quorum-sensing signal molecules have recently been proved to be involved in the interactions between bacteria and bacteriophages, which provides a possible way to solve bacteriophage infection from a population level. Finally, the rapid development of bacteriophage genome editing and synthetic biology will bring some new cues for preventing bacteriophage infection in industrial fermentation.