The mechanism of iron-compensation for manganese deficiency of Streptococcus pneumoniae
The mechanism of iron-compensation for manganese deficiency of Streptococcus pneumoniae
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肺炎链球菌缺锰的铁补偿机制
DOI：
10.1016/j.jprot.2018.06.004
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发表时间：
2018-07-30
影响因子：
3.3
通讯作者：
Sun, Xuesong
中科院分区：
文献类型：
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作者：
Cao, Kun;Lai, Fubin;Sun, Xuesong
考虑到它们参与催化、感染和生物膜的形成，铁和锰对细菌的生存和毒力是必不可少的。在本研究中，我们发现肺炎链球菌（S. pneumoniae）可以在缺锰培养基（MDCM）中生长。此外，研究结果表明，随着Mn浓度的降低，细菌中的Fe浓度升高。此外，在MDCM中添加铁可以恢复细菌的生长。采用稳定同位素二甲基标记的定量蛋白质组学方法研究了肺炎链球菌在缺锰条件下的适应性生长机制。结果发现，在MDCM中生长的肺炎链球菌有25个蛋白表达下调，而54个蛋白表达上调。研究还指出，一些下调的蛋白质参与细胞能量代谢、氨基酸合成和氧化产物的还原。更重要的是，与铁摄取相关的几个atp结合盒转运蛋白，如PiuA、PiaA、PitA和SPD_1609，由于MDCM中铁摄取增加而过度表达。结果表明，锰缺乏扰乱了肺炎链球菌的多种代谢过程。此外，它引起铁对锰的补偿作用，这有利于细菌在极端环境中的生存。意义：锰和铁在肺炎链球菌代谢中的关系尚未明确。在本文中，我们认为锰限制干扰了细菌的多种代谢过程，并明显降低了ATP水平。为了在这种极端环境中生存，细菌上调了三种类型的铁离子转运体PiuABC（血红素）、PiaABC（铬铁）和PitABC (Fe3+)，以吸收足够的铁离子来应对锰缺乏。因此，本研究揭示了细菌铁对锰的代偿机制，为研究细菌铁和锰代谢的相关性提供了新的视角。
Given their involvement in catalysis, infection, and biofilm formation, Fe and Mn are essential for bacterial survival and virulence. In this study, we found that Streptococcus pneumoniae (S. pneumoniae) could grow in the Mn-deficient medium (MDCM). Furthermore, findings showed that the Fe concentration in the bacterium increased when the Mn concentration decreased. In addition, it was noted that supplementing MDCM with Fe resulted in the recovery of bacterial growth. Quantitative proteomics using stable-isotope dimethyl labeling was performed to investigate the adaptive growth mechanism of S. pneumoniae under Mn-deficient conditions. It was found that the expression levels of 25 proteins were downregulated, whereas those of 54 proteins were upregulated in S. pneumoniae grown in MDCM. It was also noted that several of the downregulated proteins were involved in cell energy metabolism, amino acid synthesis, and reduction of oxidation products. More importantly, several ATP-binding cassette transporters related to Fe uptake, such as PiuA, PiaA, PitA, and SPD_1609, were overexpressed for increased Fe uptake from the MDCM. The results suggest that Mn deficiency disturbs multiple metabolic processes in S. pneumoniae. Furthermore, it causes a compensatory effect of Fe for Mn, which is beneficial for the survival of the bacterium in extreme environments.Significance: The relationship between manganese and iron metabolism in S. pneumoniae has not been clearly revealed. In this paper, we suggest that Mn limitation disturbs multiple metabolic processes and evidently decreases the ATP level in the bacterium. In order to survive in this extreme environment, bacteria upregulated three type of Fe ion transporters PiuABC (heme), PiaABC (ferrichrome) and PitABC (Fe3+) to uptake enough Fe ions to response to Mn deficiency. Therefore, this study reveals a bacterial mechanism of Fe compensation for Mn, and provides new insight for investigating the relativeness of Fe and Mn metabolism of bacteria.