细菌c-di-AMP检测方法的研究进展

环二腺苷酸(cyclic diadenylate monophosphate, c-di-AMP)是一种广泛存在于细菌中的重要核苷酸第二信使分子,在病原体细菌,尤其是许多革兰阴性细菌中发挥着重要作用。研究表明,c-di-AMP在细菌生长、耐药性、抗应激、侵袭力和生物膜形成等方面担当不可取代的角色,同时参与激活和调节宿主的免疫反应。有关c-di-AMP的研究逐渐深入并成为微生物研究领域的热点,微生物主要通过改变其胞内外c-di-AMP的含量来调节细菌生理功能及宿主细胞免疫反应,因此对于胞内外c-di-AMP的定量研究也得到了研究者的重视。目前针对c-di-AMP的定量检测已有多种技术方法被报道,包括经常使用的HPLC/MS检测、ELISA检测,以及利用甲氧檗因的荧光检测、荧光生物传感器的c-di-AMP活细胞成像等。每种方法的检测原理、适用范围及优缺点各不相同。对现有检测方法的总结有助于对新检测手段的探索,进一步提升对c-di-AMP功能的认知。为了广泛研究c-di-AMP介导的信号通路及其生物学作用,就目前细菌c-di-AMP的检测方法的研究进展作一综述。

Advances in Detection Methods of c-di-AMP in Bacteria

Cyclic diadenylate monophosphate (c-di-AMP) is a kind of the important second messenger molecules that widely exists in bacteria and plays an important role in pathogenic bacteria, especially in many gram-negative bacteria. Studies have shown that c-di-AMP plays an irreplaceable role in bacterial growth, drug resistance, anti-stress, invasiveness, biofilm formation, and other aspects, is also involved in activating and regulating the host immune response. Research to c-di-AMP has gradually deepened and become a hot spot in microbial field research; microorganisms mainly regulate physiological function of bacteria and host cell immune response through changing intra-or-extracellular content of c-di-AMP. Therefore, the quantitative study of intra-or extracellular c-di-AMP has also attracted attention of researchers. At present, a variety of techniques have been reported for the quantitative detection of c-di-AMP, including HPLC/MS detection commonly used by researchers, ELISA detection, as well as fluorescent turn-on assay using coralyne and c-di-AMP live cell imaging by fluorescence biosensor. Each method has its own detection principle, application scope, advantage and disadvantage. Summary of the existing detection methods is conducive to explore new detection methods and will further enhance the cognition of c-di-AMP function. In order to study c-di-AMP mediated signaling pathway and its biological effects, advances in study on bacterial c-di-AMP detection methods were reviewed in this paper.