Chaudhary Vikas, Pal Aditya Kumar, Singla Mamta, Ghosh Anirban
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.
Heliyon. 2023 Apr 29;9(5):e15686. doi: 10.1016/j.heliyon.2023.e15686. eCollection 2023 May.
Cyclic-di-AMP (c-di-AMP) is an important secondary messenger molecule that plays a critical role in monitoring several important cellular processes, especially in several Gram-positive bacteria. In this study, we seek to unravel the physiological significance of the molecule c-di-AMP in under different conditions, using strains with altered c-di-AMP levels: c-di-AMP null mutant (Δ) and a c-di-AMP over-expression mutant (Δ). Our thorough analysis of the mutants revealed that the intracellular concentration of c-di-AMP could determine many basic phenotypes such as colony architecture, cell shape, cell size, membrane permeability etc. Additionally, it was shown to play a significant role in multiple stress adaptation pathways in the case of different DNA and membrane stresses. Our study also revealed how the biofilm phenotypes of cells are altered with high intracellular c-di-AMP concentration. Next, we checked how c-di-AMP contributes to antibiotic resistance or susceptibility characteristics of , which was followed by a detailed transcriptome profile analysis to reveal key genes and pathways such as translation, arginine biosynthesis, cell wall and plasma membrane are regulated by c-di-AMP in mycobacteria.
环二腺苷酸（c-di-AMP）是一种重要的第二信使分子，在监测多种重要细胞过程中发挥关键作用，尤其是在几种革兰氏阳性细菌中。在本研究中，我们试图利用c-di-AMP水平改变的菌株：c-di-AMP缺失突变体（Δ）和c-di-AMP过表达突变体（Δ），来阐明该分子在不同条件下的生理意义。我们对这些突变体的深入分析表明，c-di-AMP的细胞内浓度可以决定许多基本表型，如菌落结构、细胞形状、细胞大小、膜通透性等。此外，在不同的DNA和膜应激情况下，它在多种应激适应途径中发挥重要作用。我们的研究还揭示了细胞内c-di-AMP浓度较高时，其生物膜表型是如何改变的。接下来，我们研究了c-di-AMP如何影响的抗生素抗性或敏感性特征，随后进行了详细的转录组谱分析，以揭示分枝杆菌中翻译、精氨酸生物合成、细胞壁和质膜等关键基因和途径是如何受c-di-AMP调控的。
