The Staphylococcus aureus α-Acetolactate Synthase ALS Confers Resistance to Nitrosative Stress.
The Staphylococcus aureus α-Acetolactate Synthase ALS Confers Resistance to Nitrosative Stress.
复制标题
DOI：
10.3389/fmicb.2017.01273
复制
发表时间：
2017
影响因子：
5.2
通讯作者：
Saraiva LM
中科院分区：
文献类型：
--
作者：
Carvalho SM;de Jong A;Kloosterman TG;Kuipers OP;Saraiva LM
金黄色葡萄球菌（Staphylococcus aureus）是一种遍布全球的病原体，其定植于人类鼻腔中，并且是呼吸道和皮肤感染的主要原因。在鼻腔中，S.金黄色葡萄球菌因先天免疫效应子产生的高浓度一氧化氮（NO）而茁壮成长，并且可利用生长缓慢代谢的游离己糖，例如半乳糖。在这里，我们使用了深度测序转录组学分析（RNA-Seq）和1H-NMR来揭示S。生长在半乳糖上的金黄色葡萄球菌，鼻咽中存在的主要碳源，存活于NO的有害作用。当使用半乳糖时，金黄色葡萄球菌耐受高浓度的NO。数据表明，这种耐药性很可能是通过依赖于氨基酸（如谷氨酸、苏氨酸和支链氨基酸（BCAA））产量增加的独特代谢来实现的。此外，我们还发现，在NO胁迫下，S.金黄色葡萄球菌α-乙酰乳酸合酶（ALS）是一种重要的酶，它将丙酮酸转化为α-乙酰乳酸。ALS被提议防止细胞内酸化，促进BCAA的产生和TCA循环的激活。此外，ALS显示有助于成功感染鼠巨噬细胞。此外，ALS有助于S.金黄色葡萄球菌对β-内酰胺抗生素如甲氧西林和苯唑西林的耐受性。
Staphylococcus aureus is a worldwide pathogen that colonizes the human nasal cavity and is a major cause of respiratory and cutaneous infections. In the nasal cavity, S. aureus thrives with high concentrations of nitric oxide (NO) produced by the innate immune effectors and has available for growth slow-metabolizing free hexoses, such as galactose. Here, we have used deep sequencing transcriptomic analysis (RNA-Seq) and 1H-NMR to uncover how S. aureus grown on galactose, a major carbon source present in the nasopharynx, survives the deleterious action of NO. We observed that, like on glucose, S. aureus withstands high concentrations of NO when using galactose. Data indicate that this resistance is, most likely, achieved through a distinct metabolism that relies on the increased production of amino acids, such as glutamate, threonine, and branched-chain amino acids (BCAAs). Moreover, we found that under NO stress the S. aureus α-acetolactate synthase (ALS) enzyme, which converts pyruvate into α-acetolactate, plays an important role. ALS is proposed to prevent intracellular acidification, to promote the production of BCAAs and the activation of the TCA cycle. Additionally, ALS is shown to contribute to the successful infection of murine macrophages. Furthermore, ALS contributes to the resistance of S. aureus to beta-lactam antibiotics such as methicillin and oxacillin.