Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia, Australia.
J Bacteriol. 2012 Nov;194(22):6248-54. doi: 10.1128/JB.01393-12. Epub 2012 Sep 14.
The thiol-containing tripeptide glutathione is an important cellular constituent of many eukaryotic and prokaryotic cells. In addition to its disulfide reductase activity, glutathione is known to protect cells from many forms of physiological stress. This report represents the first investigation into the role of glutathione in the Gram-positive pathogen Streptococcus pneumoniae. We demonstrate that pneumococci import extracellular glutathione using the ABC transporter substrate binding protein GshT. Mutation of gshT and the gene encoding glutathione reductase (gor) increases pneumococcal sensitivity to the superoxide generating compound paraquat, illustrating the importance of glutathione utilization in pneumococcal oxidative stress resistance. In addition, the gshT and gor mutant strains are hypersensitive to challenge with the divalent metal ions copper, cadmium, and zinc. The importance of glutathione utilization in pneumococcal colonization and invasion of the host is demonstrated by the attenuated phenotype of the gshT mutant strain in a mouse model of infection.
含巯基的三肽谷胱甘肽是许多真核和原核细胞的重要细胞成分。除了其二硫键还原酶活性外，谷胱甘肽还已知可保护细胞免受多种形式的生理应激。本报告代表了对革兰氏阳性病原体肺炎链球菌中谷胱甘肽作用的首次研究。我们证明肺炎球菌使用 ABC 转运体底物结合蛋白 GshT 摄取细胞外谷胱甘肽。gshT 和编码谷胱甘肽还原酶（gor）的基因突变增加了肺炎球菌对超氧化物生成化合物百草枯的敏感性，表明谷胱甘肽利用在肺炎球菌氧化应激抗性中的重要性。此外，gshT 和 gor 突变株对二价金属离子铜、镉和锌的敏感性增加。gshT 突变株在感染小鼠模型中的表型减弱表明了谷胱甘肽利用在肺炎球菌定植和侵袭宿主中的重要性。
