Staphylococcus aureus Does Not Synthesize Arginine from Proline under Physiological Conditions.
Staphylococcus aureus Does Not Synthesize Arginine from Proline under Physiological Conditions.
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金黄色葡萄球菌在生理条件下不会从脯氨酸合成精氨酸。
DOI：
10.1128/jb.00018-22
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发表时间：
2022
影响因子：
3.2
通讯作者：
Bae,Taeok
中科院分区：
文献类型：
--
作者：
Jeong,Bohyun;Shah,MajidAli;Roh,Eunjung;Kim,Kyeongkyu;Park,Indal;Bae,Taeok
革兰氏阳性病原体金黄色葡萄球菌是已知的唯一通过精氨酸-脯氨酸互变途径从脯氨酸合成精氨酸的细菌，尽管其具有用于高度保守的谷氨酸途径的基因。由于脯氨酸-精氨酸互变途径受到CcpA介导的碳分解代谢物阻遏（CCR）的抑制，CCR被认为是S.金黄色。利用核糖作为次级碳源，我们证明了S。金黄色葡萄球菌精氨酸营养缺陷型不是由于CCR，而是由于脯氨酸降解产物的浓度不足。脯氨酸被脯氨酸脱氢酶（PutA）降解为吡咯啉-5-羧酸（P5 C）。尽管PutA的表达被核糖完全诱导，但P5 C的浓度仍然不足以支持精氨酸的合成，因为P5 C不断被P5 C还原酶ProC消耗。金黄色葡萄球菌能以脯氨酸为底物合成精氨酸，与碳源无关。相反，当过表达proC降低P5 C浓度时，它抑制了无精氨酸的cpA缺失突变体的生长。有趣的是，谷氨酸途径酶的异位表达转化了S。aureus转化为精氨酸原养型。在动物实验中，S.金黄色。根据这些结果，我们得出结论，S。金黄色葡萄球菌在生理条件下不从脯氨酸合成精氨酸。我们还提出精氨酸营养缺陷型的S。金黄色葡萄球菌的致病性不是由于CcpA介导的CCR，而是由于保守的谷氨酸途径的失活。重要提示金黄色葡萄球菌是一种多功能的革兰氏阳性人类病原体，感染各种人体器官。该细菌的多功能性部分归因于通过碳分解代谢物抑制系统（CCR）进行的有效代谢调节。S.已知金黄色葡萄球菌可使脯氨酸和精氨酸相互转化，CCR抑制这两种氨基酸的合成。然而，当CCR由非优选碳源释放时，S.金黄色葡萄球菌能合成脯氨酸，但不能合成精氨酸。在这项研究中，我们表明，在S。在金黄色葡萄球菌中，脯氨酸的降解产物和脯氨酸合成的底物吡咯啉-5-羧酸（P5 C）的细胞内浓度太低而不能从脯氨酸合成精氨酸。这些结果对S.金黄色葡萄球菌从脯氨酸合成精氨酸。
The Gram-positive pathogen Staphylococcus aureus is the only bacterium known to synthesize arginine from proline via the arginine-proline interconversion pathway despite having genes for the well-conserved glutamate pathway. Since the proline-arginine interconversion pathway is repressed by CcpA-mediated carbon catabolite repression (CCR), CCR has been attributed to the arginine auxotrophy of S. aureus. Using ribose as a secondary carbon source, here, we demonstrate that S. aureus arginine auxotrophy is not due to CCR but due to the inadequate concentration of proline degradation product. Proline is degraded by proline dehydrogenase (PutA) into pyrroline-5-carboxylate (P5C). Although the PutA expression was fully induced by ribose, the P5C concentration remained insufficient to support arginine synthesis because P5C was constantly consumed by the P5C reductase ProC. When the P5C concentration was artificially increased by either PutA overexpression orproCdeletion, S. aureus could synthesize arginine from proline regardless of carbon source. In contrast, when the P5C concentration was reduced by overexpression ofproC, it inhibited the growth of theccpAdeletion mutant without arginine. Intriguingly, the ectopic expression of the glutamate pathway enzymes converted S. aureus into arginine prototroph. In an animal experiment, the arginine-proline interconversion pathway was not required for the survival of S. aureus. Based on these results, we concluded that S. aureus does not synthesize arginine from proline under physiological conditions. We also propose that arginine auxotrophy of S. aureus is not due to the CcpA-mediated CCR but due to the inactivity of the conserved glutamate pathway.IMPORTANCEStaphylococcus aureus is a versatile Gram-positive human pathogen infecting various human organs. The bacterium's versatility is partly due to efficient metabolic regulation via the carbon catabolite repression system (CCR). S. aureus is known to interconvert proline and arginine, and CCR represses the synthesis of both amino acids. However, when CCR is released by a nonpreferred carbon source, S. aureus can synthesize proline but not arginine. In this study, we show that, in S. aureus, the intracellular concentration of pyrroline-5-carboxylate (P5C), the degradation product of proline and the substrate of proline synthesis, is too low to synthesize arginine from proline. These results call into question the notion that S. aureus synthesizes arginine from proline.