Transcription Regulation Lab, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad, 121001, India; Kalinga Institute of Industrial Technology, Bhubaneswar, Odisha, 751024, India.
Transcription Regulation Lab, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad, 121001, India.
Mol Aspects Med. 2021 Oct;81:101001. doi: 10.1016/j.mam.2021.101001. Epub 2021 Jul 24.
Pseudomonas aeruginosa is an opportunistic human pathogen and is the primary cause of nosocomial infections. Biofilm formation by this organism results in chronic and hard to eradicate infections. The intracellular signalling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a secondary messenger in bacterial cells crucial for motile to sessile transition. The signalling pathway components encompass two classes of enzymes with antagonistic activities, the diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) that regulate the cellular levels of c-di-GMP at distinct stages of biofilm initiation, maturation and dispersion. This review summarizes the structural analysis and functional studies of the DGCs and PDEs involved in biofilm regulation in P. aeruginosa. In addition, we also describe the effector proteins that sense the perturbations in c-di-GMP levels to elicit a functional output. Finally, we discuss possible mechanisms that allow the dynamic levels of c-di-GMP to regulate cognate cellular response. Uncovering the details of the regulation of the c-di-GMP signalling pathway is vital for understanding the behaviour of the pathogen and characterization of novel targets for anti-biofilm interventions.
铜绿假单胞菌是一种机会性病原体，是医院获得性感染的主要原因。该生物体形成生物膜导致慢性和难以根除的感染。胞内信号分子双-(3'-5')-环二鸟苷单磷酸(c-di-GMP)是细菌细胞中一种重要的第二信使，对于从运动到静止的转换至关重要。信号通路成分包括两类具有拮抗活性的酶，即环二鸟苷酸环化酶(DGCs)和磷酸二酯酶(PDEs)，它们在生物膜起始、成熟和分散的不同阶段调节细胞内 c-di-GMP 的水平。这篇综述总结了参与铜绿假单胞菌生物膜调节的 DGCs 和 PDEs 的结构分析和功能研究。此外，我们还描述了感应 c-di-GMP 水平变化以产生功能输出的效应蛋白。最后，我们讨论了允许 c-di-GMP 动态水平调节同源细胞反应的可能机制。揭示 c-di-GMP 信号通路的调节细节对于理解病原体的行为和表征新型抗生物膜干预靶点至关重要。
