Dynamic Polyphosphate Metabolism Coordinating with Manganese Ions Defends against Oxidative Stress in the Extreme Bacterium Deinococcus radiodurans
Dynamic Polyphosphate Metabolism Coordinating with Manganese Ions Defends against Oxidative Stress in the Extreme Bacterium Deinococcus radiodurans
复制标题
与锰离子协调的动态多磷酸代谢可抵抗极端细菌耐辐射球菌的氧化应激
DOI：
10.1128/aem.02785-20
复制
发表时间：
2021-04-01
影响因子：
4.4
通讯作者：
Tian, Bing
中科院分区：
文献类型：
--
作者：
Dai, Shang;Xie, Zhenming;Tian, Bing
锰-磷酸盐复合物（Mn-Pi）在耐辐射细菌的细胞抗性中起着关键作用。进化上古老的聚磷酸盐聚合物（聚磷酸盐[PolyP]）可以有效地螯合Mn2+并提供磷酸盐。摘要耐辐射异常球菌是一种极端细菌，具有无与伦比的抗氧化能力。胞内Mn~（2+）与小分子代谢产物络合物的积累是D.抗氧化应激。然而，胞内锰离子库和锰络合物的稳态调节在D。抗辐射物质仍不清楚。我们在D.耐辐射的我们研究了D.抗辐射剂对氧化应激的影响dr1939基因编码多聚磷酸酶激酶（PPKDr;下标Dr指D.和dra0185，编码外聚磷酸酶（PPXDr）。PPXDr是一种新型的外切多聚磷酸酶，具有对Mn2+的辅因子偏好，其增强PPXDr的二聚化和活性以允许有效切割PolyP-Mn。PPKDr和PPXDr在氧化应激下表现出不同的动态表达谱。首先，ppkDr被上调，导致PolyP的积累，其螯合大量的细胞内Mn离子。随后，ppkDr的表达水平下降，而ppxDr被大幅上调，并有效水解无活性的PolyP-Mn以释放磷酸盐（Pi）和Mn2+，其可以形成Mn-Pi复合物以吸收O2 −并保护蛋白质免受氧化损伤。因此，与游离Mn离子复合的动态细胞PolyP代谢物突出了D.抗辐射剂对氧化应激的反应。锰-磷酸盐复合物（Mn-Pi）在耐辐射细菌的细胞抗性中起着关键作用。进化上古老的聚磷酸盐聚合物（聚磷酸盐[PolyP]）可以有效地螯合Mn2+并提供磷酸盐。然而，锰离子的细胞内储库和Mn-Pi复合物的稳态调节仍不清楚。在这里，我们研究了PolyP代谢产物和Mn2+稳态的关系，以及它们如何在耐辐射细菌Deinococcus radiodurans中抵御氧化应激。我们发现PPXDr（下标Dr是指D. Radiodurans）是一种新型的外切多聚磷酸酶，具有对Mn 2+的辅因子偏好，介导PolyP-Mn降解成Pi和Mn离子。形成的Mn-Pi复合物有效地保护蛋白质。PolyP与Mn离子的动态协同代谢是D.抗辐射剂对氧化应激的反应。这一发现不仅为极端细菌D.同时也拓宽了我们对PolyP代谢在生物体中的功能的理解。
The Mn-phosphate complex (Mn-Pi) plays a key role in the cellular resistance of radioresistant bacteria. The evolutionarily ancient polyphosphate polymers (polyphosphate [PolyP]) could effectively chelate Mn2+ and donate phosphates. ABSTRACT Deinococcus radiodurans is an extreme bacterium with unparalleled resistance to oxidative stresses. Accumulation of intracellular Mn2+ complexing with small metabolites is the key contributor to the tolerance of D. radiodurans against oxidative stress. However, the intracellular reservoir of Mn ions and homeostatic regulation of the Mn complex in D. radiodurans remain unclear. We identified an evolutionarily ancient and negatively charged phosphate polymer (polyphosphate [PolyP]) in D. radiodurans. We investigated PolyP metabolism in the response of D. radiodurans to oxidative stress. The genes dr1939, encoding polyphosphatase kinase (PPKDr; the subscript “Dr” refers to D. radiodurans), and dra0185, encoding exopolyphosphatase (PPXDr), were identified. PPXDr is a novel exopolyphosphatase with a cofactor preference to Mn2+, which enhances the dimerization and activity of PPXDr to allow the effective cleavage of PolyP-Mn. PPKDr and PPXDr exhibited different dynamic expression profiles under oxidative stress. First, ppkDr was upregulated leading to the accumulation of PolyP, which chelated large amounts of intracellular Mn ions. Subsequently, the expression level of ppkDr decreased while ppxDr was substantially upregulated and effectively hydrolyzed inactive PolyP-Mn to release phosphate (Pi) and Mn2+, which could form into Mn-Pi complexes to scavenge O2− and protect proteins from oxidative damage. Hence, dynamic cellular PolyP metabolites complexed with free Mn ions highlight a defense strategy of D. radiodurans in response to oxidative stress. IMPORTANCE The Mn-phosphate complex (Mn-Pi) plays a key role in the cellular resistance of radioresistant bacteria. The evolutionarily ancient polyphosphate polymers (polyphosphate [PolyP]) could effectively chelate Mn2+ and donate phosphates. However, the intracellular reservoir of Mn ions and homeostatic regulation of the Mn-Pi complex remain unclear. Here, we investigated the relationship of PolyP metabolites and Mn2+ homeostasis and how they function to defend against oxidative stress in the radioresistant bacterium Deinococcus radiodurans. We found that PPXDr (the subscript “Dr” refers to D. radiodurans) is a novel exopolyphosphatase with a cofactor preference for Mn2+, mediating PolyP-Mn degradation into Pi and Mn ions. The formed Mn-Pi complexes effectively protect proteins. The dynamic PolyP metabolism coordinating with Mn ions is a defense strategy of D. radiodurans in response to oxidative stress. The findings not only provide new insights into the resistance mechanism of the extreme bacterium D. radiodurans but also broaden our understanding of the functions of PolyP metabolism in organisms.