Zhu Xifang, Baranowski Eric, Hao Zhiyu, Li Xixi, Zhao Gang, Dong Yaqi, Chen Yingyu, Hu Changmin, Chen Huanchun, Citti Christine, Wang Aiping, Guo Aizhen
School of Life Sciences, Zhengzhou University, Zhengzhou, China.
Longhu Laboratory of Advanced Immunology, Zhengzhou, China.
Front Microbiol. 2023 Nov 30;14:1250368. doi: 10.3389/fmicb.2023.1250368. eCollection 2023.
Nucleotide second messengers play an important role in bacterial adaptation to environmental changes. Recent evidence suggests that some of these regulatory molecular pathways were conserved upon the degenerative evolution of the wall-less mycoplasmas. We have recently reported the occurrence of a phosphodiesterase (PDE) in the ruminant pathogen , which was involved in c-di-AMP metabolism. In the present study, we demonstrate that the genome of this mycoplasma species encodes a PDE of the GdpP family with atypical DHH domains. Characterization of GdpP (MbovGdpP) revealed a multifunctional PDE with unusual nanoRNase and single-stranded DNase activities. The alarmone ppGpp was found unable to inhibit c-di-NMP degradation by MbovGdpP but efficiently blocked its nanoRNase activity. Remarkably, MbovGdpP was found critical for the osmotic tolerance of under K and Na conditions. Transcriptomic analyses further revealed the biological importance of MbovGdpP in tRNA biosynthesis, pyruvate metabolism, and several steps in genetic information processing. This study is an important step in understanding the role of PDE and nucleotide second messengers in the biology of a minimal bacterial pathogen.
核苷酸第二信使在细菌适应环境变化中发挥着重要作用。最近的证据表明，其中一些调节分子途径在无壁支原体的退化进化过程中得以保留。我们最近报道了反刍动物病原体中一种磷酸二酯酶（PDE）的存在，它参与了环二腺苷酸（c-di-AMP）的代谢。在本研究中，我们证明该支原体物种的基因组编码一种具有非典型DHH结构域的GdpP家族磷酸二酯酶。对GdpP（MbovGdpP）的表征揭示了一种具有异常纳米核糖核酸酶和单链脱氧核糖核酸酶活性的多功能磷酸二酯酶。发现警报素鸟苷四磷酸（ppGpp）无法抑制MbovGdpP对环二核苷酸（c-di-NMP）的降解，但能有效阻断其纳米核糖核酸酶活性。值得注意的是，发现MbovGdpP对该支原体在钾离子和钠离子条件下的渗透压耐受性至关重要。转录组分析进一步揭示了MbovGdpP在转运RNA（tRNA）生物合成、丙酮酸代谢以及遗传信息处理的几个步骤中的生物学重要性。这项研究是理解磷酸二酯酶和核苷酸第二信使在最小细菌病原体生物学中作用的重要一步。
