胁迫诱导抗性基因转移导致细菌耐药的分子机制研究进展

Advances in molecular mechanisms of bacterial resistance caused by stress-induced transfer of resistance genes—A review

抗性基因转移是细菌形成耐药性的重要原因。近年来的研究表明胁迫因子可通过多种机制诱导抗性基因转移。DNA损伤可导致细菌产生SOS应激反应,进而诱导接合DNA介导的抗性基因转移。在一些缺乏SOS系统的细菌中,抗生素胁迫可诱导细菌建立自然转化感受态。此外,作者最近的研究表明普通胁迫应答因子RpoS调控一种由双链质粒DNA介导的固体基质表面的抗性基因转移方式。本文在总结SOS依赖和非依赖型胁迫因子诱导细菌接合和转化介导的DNA转移以及RpoS调控固体基质表面双链质粒DNA转移的基础上,提出今后需重点研究胁迫因子如何激活关键调控蛋白以及这些调控蛋白如何影响DNA转移相关基因表达等关键问题。解决上述问题将为寻找合适的分子靶标用于防控抗性基因转移导致的细菌耐药奠定基础。

The transfer of resistance gene is one of the most important causes of bacterial resistance. Recent studies reveal that stresses induce the transfer of antibiotic resistance gene through multiple mechanisms. DNA damage stresses trigger bacterial SOS response and induce the transfer of resistance gene mediated by conjugative DNA. Antibiotic stresses induce natural bacterial competence for transformation in some bacteria which lack the SOS system. In addition, our latest studies show that the general stress response regulator RpoS regulates a novel type of resistance gene transfer which is mediated by double-stranded plasmid DNA and occurs exclusively on the solid surface. In this review, we summarized recent advances in SOS dependent and independent stress-induced DNA transfer which is mediated by conjugation and transformation respectively, and the transfer of double-stranded plasmid DNA on the solid surface which is regulated by RpoS. We propose that future work should address how stresses activate the key regulators and how these regulators control the expression of gene transfer related genes. Answers to the above questions would pave the way for searching for candidate targets for controlling bacterial resistance resulted from the transfer of antibiotic genes.