Cysteine Biosynthesis in Campylobacter jejuni: Substrate Specificity of CysM and the Dualism of Sulfide.
Cysteine Biosynthesis in Campylobacter jejuni: Substrate Specificity of CysM and the Dualism of Sulfide.
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弯曲杆菌空肠中的半胱氨酸生物合成：Cysm的底物特异性和硫化物的二元论。
DOI：
10.3390/biom13010086
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发表时间：
2022-12-31
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
空肠弯曲杆菌是一种非常成功的肠道病原体，具有小型、适应宿主的基因组（1.64 Mbp，约 1650 个编码基因）。因此，空肠弯曲菌在许多代谢途径（包括硫代谢）中的能力有限。由于无法利用离子硫，空肠弯曲菌依靠摄取外源半胱氨酸及其衍生物来供应这种必需氨基酸。半胱氨酸也可以由唯一的半胱氨酸合酶 CysM 从头合成。在这项研究中，我们探索了纯化的空肠弯曲菌CysM的底物特异性，并将其定义为O-乙酰基-L-丝氨酸硫化氢解酶，几乎绝对偏好硫化物作为硫供体。空肠弯曲菌定殖的肠道生态位中会产生大量硫化物，但硫化物通常被认为对细菌具有剧毒。我们在限硫培养基中进行了一系列生长实验，证明硫化物在生理相关浓度下是空肠弯曲杆菌极好的硫源，驳斥了硫化物作为对细菌纯粹有害的化合物的观点。尽管如此，空肠弯曲菌确实受到浓度升高的硫化物的抑制，我们试图了解所涉及的靶点。令人惊讶的是，我们发现硫化物敏感的初级末端氧化酶（cbb3型细胞色素c氧化酶CcoNOPQ）的失活并不能解释硫化物对生长的大部分抑制。因此，需要进一步的工作来揭示空肠弯曲菌中硫化物毒性的细胞靶标。
Campylobacter jejuni is a highly successful enteric pathogen with a small, host-adapted genome (1.64 Mbp, ~1650 coding genes). As a result, C. jejuni has limited capacity in numerous metabolic pathways, including sulfur metabolism. Unable to utilise ionic sulfur, C. jejuni relies on the uptake of exogenous cysteine and its derivatives for its supply of this essential amino acid. Cysteine can also be synthesized de novo by the sole cysteine synthase, CysM. In this study, we explored the substrate specificity of purified C. jejuni CysM and define it as an O-acetyl-L-serine sulfhydrylase with an almost absolute preference for sulfide as sulfur donor. Sulfide is produced in abundance in the intestinal niche C. jejuni colonises, yet sulfide is generally viewed as highly toxic to bacteria. We conducted a series of growth experiments in sulfur-limited media and demonstrate that sulfide is an excellent sulfur source for C. jejuni at physiologically relevant concentrations, combating the view of sulfide as a purely deleterious compound to bacteria. Nonetheless, C. jejuni is indeed inhibited by elevated concentrations of sulfide and we sought to understand the targets involved. Surprisingly, we found that inactivation of the sulfide-sensitive primary terminal oxidase, the cbb3-type cytochrome c oxidase CcoNOPQ, did not explain the majority of growth inhibition by sulfide. Therefore, further work is required to reveal the cellular targets responsible for sulfide toxicity in C. jejuni.
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