School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK.
School of Biological Sciences, University of Reading, Reading RG6 6AX, UK.
Biomolecules. 2022 Dec 31;13(1):86. doi: 10.3390/biom13010086.
is a highly successful enteric pathogen with a small, host-adapted genome (1.64 Mbp, ~1650 coding genes). As a result, has limited capacity in numerous metabolic pathways, including sulfur metabolism. Unable to utilise ionic sulfur, 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 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 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 at physiologically relevant concentrations, combating the view of sulfide as a purely deleterious compound to bacteria. Nonetheless, 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 -type cytochrome 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 .
是一种非常成功的肠道病原体，其基因组较小且适应宿主（1.64 Mbp，约 1650 个编码基因）。因此，在许多代谢途径中，包括硫代谢，都有能力有限。无法利用离子硫，依赖于摄取外源性半胱氨酸及其衍生物来提供这种必需氨基酸。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 CysM 的底物特异性，并将其定义为 O-乙酰-L-丝氨酸硫基酶，对硫供体几乎有绝对的偏好。在 定殖的肠道生态位中大量产生硫化物，但通常认为硫化物对细菌具有高度毒性。我们在硫限制培养基中进行了一系列生长实验，证明硫化物是生理相关浓度下的极好硫源，这与将硫化物视为对细菌纯粹有害的化合物的观点相矛盾。尽管如此，硫化物确实会抑制 的生长，我们试图了解涉及的靶标。令人惊讶的是，我们发现，对硫化物敏感的初级末端氧化酶，-型细胞色素氧化酶 CcoNOPQ 的失活并不能解释硫化物对生长的大部分抑制作用。因此，需要进一步的工作来揭示细胞靶标负责硫化物毒性在 。
