State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana, USA.
Appl Environ Microbiol. 2021 Feb 26;87(6). doi: 10.1128/AEM.02261-20.
GW4 is a heterotrophic arsenite-oxidizing bacterium with a high resistance to arsenic toxicity. It is now a model organism for studying the processes of arsenic detoxification and utilization. Previously, we demonstrated that under low-phosphate conditions, arsenate [As(V)] could enhance bacterial growth and be incorporated into biomolecules, including lipids. While the basic microbial As(V) resistance mechanisms have been characterized, global metabolic responses under low phosphate remain largely unknown. In the present work, the impacts of As(V) and low phosphate on intracellular metabolite and lipid profiles of GW4 were quantified using liquid chromatography-mass spectroscopy (LC-MS) in combination with transcriptional assays and the analysis of intracellular ATP and NADH levels. Metabolite profiling revealed that oxidative stress response pathways were altered and suggested an increase in DNA repair. Changes in metabolite levels in the tricarboxylic acid (TCA) cycle along with increased ATP are consistent with As(V)-enhanced growth of GW4. Lipidomics analysis revealed that most glycerophospholipids decreased in abundance when As(V) was available. However, several glycerolipid classes increased, an outcome that is consistent with maximizing growth via a phosphate-sparing phenotype. Differentially regulated lipids included phosphotidylcholine and lysophospholipids, which have not been previously reported in The metabolites and lipids identified in this study deepen our understanding of the interplay between phosphate and arsenate on chemical and metabolic levels. Arsenic is widespread in the environment and is one of the most ubiquitous environmental pollutants. Parodoxically, the growth of certain bacteria is enhanced by arsenic when phosphate is limited. Arsenate and phosphate are chemically similar, and this behavior is believed to represent a phosphate-sparing phenotype in which arsenate is used in place of phosphate in certain biomolecules. The research presented here uses a global approach to track metabolic changes in an environmentally relevant bacterium during exposure to arsenate when phosphate is low. Our findings are relevant for understanding the environmental fate of arsenic as well as how human-associated microbiomes respond to this common toxin.
GW4 是一种异养亚砷酸盐氧化细菌，对砷毒性具有很高的抵抗力。它现在是研究砷解毒和利用过程的模式生物。以前，我们证明在低磷条件下，砷酸盐[As(V)]可以增强细菌的生长并被整合到生物分子中，包括脂质。虽然已经描述了基本的微生物 As(V)抗性机制，但低磷酸盐下的全局代谢反应在很大程度上仍然未知。在本工作中，使用液相色谱-质谱联用 (LC-MS) 结合转录分析以及细胞内 ATP 和 NADH 水平的分析，定量了 As(V)和低磷对 GW4 细胞内代谢物和脂质谱的影响。代谢物谱分析表明，氧化应激反应途径发生了改变，并表明 DNA 修复增加。三羧酸 (TCA) 循环中代谢物水平的变化以及 ATP 的增加与 GW4 中 As(V)增强的生长一致。脂质组学分析表明，当有 As(V)时，大多数甘油磷脂的丰度降低。然而，几种甘油脂类增加，这一结果与通过节省磷酸盐的表型最大化生长一致。差异调节的脂质包括磷脂酰胆碱和溶血磷脂，以前在 GW4 中没有报道过。本研究中鉴定的代谢物和脂质加深了我们对磷酸盐和砷酸盐在化学和代谢水平上相互作用的理解。砷在环境中广泛存在，是最普遍的环境污染物之一。矛盾的是，当磷酸盐有限时，某些细菌的生长会因砷而增强。砷酸盐和磷酸盐在化学上相似，这种行为被认为代表了一种节省磷酸盐的表型，其中在某些生物分子中使用砷酸盐代替磷酸盐。本研究使用全局方法来跟踪在低磷条件下暴露于砷酸盐时，一种环境相关细菌的代谢变化。我们的发现对于理解砷的环境命运以及与人类相关的微生物组如何应对这种常见毒素具有重要意义。
