The glutathione import system satisfies the Staphylococcus aureus nutrient sulfur requirement and promotes interspecies competition.
The glutathione import system satisfies the Staphylococcus aureus nutrient sulfur requirement and promotes interspecies competition.
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DOI：
10.1371/journal.pgen.1010834
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发表时间：
2023-07
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
硫是细菌增殖不可缺少的元素。先前的研究表明，人类病原体金黄色葡萄球菌利用谷胱甘肽（GSH）作为营养硫的来源;然而，GSH获取的机制尚未确定。在这里，我们确定了一个五基因位点，包括一个推定的ABC转运蛋白和预测的γ-谷氨酰转肽酶（ggt），促进S。金黄色葡萄球菌增殖在补充有还原型或氧化型GSH（GSSG）作为营养硫的唯一来源的培养基中。基于这些表型，我们将这种转运操纵子命名为谷胱甘肽输入系统（gisABCD）。Ggt在gisBCD操纵子内编码，并且我们表明该酶能够使用GSH或GSSG作为底物释放谷氨酸，证明它是真正的γ-谷氨酰转肽酶。我们还确定Ggt在细胞质中表达，仅代表细胞质Ggt定位的第二个例子，另一个是脑膜炎奈瑟菌。生物信息学分析表明，与S.金黄色葡萄球菌编码GisABCD-Ggt同源物。然而，在表皮葡萄球菌中未检测到同源系统。因此，我们建立GisABCD-Ggt提供了一个竞争优势的S。金黄色葡萄球菌相对于S.表皮中的GSH和GSSG依赖性的方式。总之，本研究描述了在S.金黄色葡萄球菌，其除了GSH之外还靶向GSSG，并促进与通常与人类微生物群相关的其他葡萄球菌的竞争。谷胱甘肽（GSH）是一种存在于哺乳动物组织中的丰富的含硫抗氧化剂。因此，它是人类病原体如金黄色葡萄球菌的营养硫的潜在来源。但S.金黄色葡萄球菌谷胱甘肽的获取尚未定义。在此，我们描述了一种支持S.金黄色葡萄球菌在补充有还原型或氧化型（GSSG）GSH的培养基中培养，我们将其命名为GSH输入系统或GisABCD。我们确定GSH和GSSG可以被GGT分解代谢，并证明该酶存在于葡萄球菌细胞质内，表明GSH和GSSG是完整导入的。最后，我们发现，GisABCD-Ggt促进竞争，表皮葡萄球菌在GSH和GSSG依赖的方式，证明GisABCD-Ggt促进营养硫收购之间的细菌。
Sulfur is an indispensable element for bacterial proliferation. Prior studies demonstrated that the human pathogen Staphylococcus aureus utilizes glutathione (GSH) as a source of nutrient sulfur; however, mechanisms of GSH acquisition are not defined. Here, we identify a five-gene locus comprising a putative ABC-transporter and predicted γ–glutamyl transpeptidase (ggt) that promotes S. aureus proliferation in medium supplemented with either reduced or oxidized GSH (GSSG) as the sole source of nutrient sulfur. Based on these phenotypes, we name this transporter operon the glutathione import system (gisABCD). Ggt is encoded within the gisBCD operon, and we show that the enzyme is capable of liberating glutamate using either GSH or GSSG as substrates, demonstrating it is a bona fide γ–glutamyl transpeptidase. We also determine that Ggt is expressed in the cytoplasm, representing only the second example of cytoplasmic Ggt localization, the other being Neisseria meningitidis. Bioinformatic analyses revealed that Staphylococcus species closely related to S. aureus encode GisABCD-Ggt homologs. However, homologous systems were not detected in Staphylococcus epidermidis. Consequently, we establish that GisABCD-Ggt provides a competitive advantage for S. aureus over S. epidermidis in a GSH- and GSSG-dependent manner. Overall, this study describes the discovery of a nutrient sulfur acquisition system in S. aureus that targets GSSG in addition to GSH and promotes competition against other staphylococci commonly associated with the human microbiota. Glutathione (GSH) is an abundant sulfur-containing antioxidant present in mammalian tissues. As such, it is a potential source of nutrient sulfur for human pathogens like Staphylococcus aureus. However, mechanisms of S. aureus GSH acquisition are undefined. Herein, we describe a transport system that supports proliferation of S. aureus in medium supplemented with reduced or oxidized (GSSG) GSH and we name it the GSH import system or GisABCD. We determine that GSH and GSSG can be catabolized by Ggt and demonstrate that the enzyme resides within the staphylococcal cytoplasm, indicating that GSH and GSSG are imported intact. Lastly, we reveal that GisABCD-Ggt facilitates competition over Staphylococcus epidermidis in a GSH- and GSSG-dependent manner, demonstrating GisABCD-Ggt promotes nutrient sulfur acquisition between commensal bacteria.
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影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
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5.8
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Gardner, Shea N.;Slezak, Tom;Hall, Barry G.
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影响因子：
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影响因子：
2.6
作者：
Bae, T;Schneewind, O
通讯作者：
Schneewind, O
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6.4
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Brouwer, Stephan;Jespersen, Magnus G.;Ong, Cheryl-Lynn Y.;De Oliveira, David M. P.;Keller, Bernhard;Cork, Amanda J.;Djoko, Karrera Y.;Davies, Mark R.;Walker, Mark J.
通讯作者：
Walker, Mark J.