Department of Biosciences, Durham University, Durham DH1 3LE, UK.
Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Metallomics. 2023 Nov 2;15(11). doi: 10.1093/mtomcs/mfad064.
All bacteria possess homeostastic mechanisms that control the availability of micronutrient metals within the cell. Cross-talks between different metal homeostasis pathways within the same bacterial organism have been reported widely. In addition, there have been previous suggestions that some metal uptake transporters can promote adventitious uptake of the wrong metal. This work describes the cross-talk between Cu and the Zn and Mn homeostasis pathways in Group A Streptococcus (GAS). Using a ∆copA mutant strain that lacks the primary Cu efflux pump and thus traps excess Cu in the cytoplasm, we show that growth in the presence of supplemental Cu promotes downregulation of genes that contribute to Zn or Mn uptake. This effect is not associated with changes in cellular Zn or Mn levels. Co-supplementation of the culture medium with Zn or, to a lesser extent, Mn alleviates key Cu stress phenotypes, namely bacterial growth and secretion of the fermentation end-product lactate. However, neither co-supplemental Zn nor Mn influences cellular Cu levels or Cu availability in Cu-stressed cells. In addition, we provide evidence that the Zn or Mn uptake transporters in GAS do not promote Cu uptake. Together, the results from this study strengthen and extend our previous proposal that mis-regulation of Zn and Mn homeostasis is a key phenotype of Cu stress in GAS.
所有细菌都拥有体内维持微量元素金属稳态的机制。同一细菌体内不同金属稳态途径之间的交流已被广泛报道。此外，先前有研究表明，一些金属摄取转运蛋白可能会促进错误金属的偶然摄取。本研究描述了 A 组链球菌（GAS）中 Cu 与 Zn 和 Mn 稳态途径之间的交流。利用缺乏主要 Cu 外排泵的 ∆copA 突变株，该突变株会使过量的 Cu 滞留在细胞质中，我们发现，在补充 Cu 的存在下生长会促进参与 Zn 或 Mn 摄取的基因下调。这种效应与细胞内 Zn 或 Mn 水平的变化无关。培养基的共补充 Zn 或在较小程度上补充 Mn 可以缓解关键的 Cu 应激表型，即细菌生长和发酵终产物乳酸的分泌。然而，共补充 Zn 或 Mn 均不影响 Cu 应激细胞中的细胞内 Cu 水平或 Cu 的可用性。此外，我们提供了证据表明 GAS 中的 Zn 或 Mn 摄取转运蛋白不会促进 Cu 的摄取。总的来说，本研究的结果加强并扩展了我们之前的观点，即 Zn 和 Mn 稳态失调是 GAS 中 Cu 应激的一个关键表型。
