Institut Für Med. Mikrobiologie und Hygiene, Elfriede-Aulhorn-Straße 6, 72076, Tübingen, Germany.
Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.
Sci Rep. 2021 May 6;11(1):9651. doi: 10.1038/s41598-021-88646-1.
Stapylococcus aureus colonises the nose of healthy individuals but can also cause a wide range of infections. Amino acid (AA) synthesis and their availability is crucial to adapt to conditions encountered in vivo. Most S. aureus genomes comprise all genes required for AA biosynthesis. Nevertheless, different strains require specific sets of AAs for growth. In this study we show that regulation inactivates pathways under certain conditions which result in these observed auxotrophies. We analyzed in vitro and modeled in silico in a Boolean semiquantitative model (195 nodes, 320 edges) the regulatory impact of stringent response (SR) on AA requirement in S. aureus HG001 (wild-type) and in mutant strains lacking the metabolic regulators RSH, CodY and CcpA, respectively. Growth in medium lacking single AAs was analyzed. Results correlated qualitatively to the in silico predictions of the final model in 92% and quantitatively in 81%. Remaining gaps in our knowledge are evaluated and discussed. This in silico model is made fully available and explains how integration of different inputs is achieved in SR and AA metabolism of S. aureus. The in vitro data and in silico modeling stress the role of SR and central regulators such as CodY for AA metabolisms in S. aureus.
金黄色葡萄球菌定植于健康个体的鼻腔，但也可引起广泛的感染。氨基酸（AA）的合成及其可用性对适应体内遇到的条件至关重要。大多数金黄色葡萄球菌基因组包含 AA 生物合成所需的所有基因。然而，不同的菌株需要特定的 AA 集来生长。在这项研究中，我们表明，在某些条件下，调节会使途径失活，从而导致这些观察到的营养缺陷。我们分析了金黄色葡萄球菌 HG001（野生型）和分别缺乏代谢调节剂 RSH、CodY 和 CcpA 的突变株在体外的生长情况，并在布尔半定量模型（195 个节点，320 个边）中对严格响应（SR）对 AA 需求的调节影响进行了建模。分析了在缺乏单个 AA 的培养基中的生长情况。结果与最终模型的计算机预测在定性上相关（92%），在定量上相关（81%）。我们评估并讨论了知识中的剩余差距。该计算机模型已完全可用，并解释了 SR 和金黄色葡萄球菌 AA 代谢中如何实现不同输入的整合。体外数据和计算机模拟强调了 SR 和中央调节剂（如 CodY）在金黄色葡萄球菌 AA 代谢中的作用。
