Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom.
Infect Immun. 2010 Dec;78(12):5223-32. doi: 10.1128/IAI.00762-10. Epub 2010 Sep 27.
The Gram-positive bacterium Staphylococcus aureus contains two glyceraldehyde-3-phosphate dehydrogenase (GAPDH) homologues known as GapA and GapB. GapA has been characterized as a functional GAPDH protein, but currently there is no biological evidence for the role of GapB in metabolism in S. aureus. In this study we show through a number of complementary methods that S. aureus GapA is essential for glycolysis while GapB is essential in gluconeogenesis. These proteins are reciprocally regulated in response to glucose concentrations, and both are influenced by the glycolysis regulator protein GapR, which is the first demonstration of the role of this regulator in S. aureus and the first indication that GapR homologues control genes other than those within the glycolytic operon. Furthermore, we show that both GapA and GapB are important in the pathogenesis of S. aureus in a Galleria mellonella model of infection, showing for the first time in any bacteria that both glycolysis and gluconeogenesis have important roles in virulence.
革兰氏阳性菌金黄色葡萄球菌含有两种甘油醛-3-磷酸脱氢酶(GAPDH)同源物,分别称为 GapA 和 GapB。GapA 已被确认为具有功能的 GAPDH 蛋白,但目前尚无生物学证据表明 GapB 在金黄色葡萄球菌的代谢中发挥作用。在这项研究中,我们通过多种互补的方法表明,金黄色葡萄球菌 GapA 是糖酵解所必需的,而 GapB 则是糖异生所必需的。这些蛋白在葡萄糖浓度的响应下相互调节,并且都受到糖酵解调节蛋白 GapR 的影响,这首次证明了该调节蛋白在金黄色葡萄球菌中的作用,也首次表明 GapR 同源物除了控制糖酵解操纵子内的基因外,还控制其他基因。此外,我们在金龟子幼虫感染模型中表明,GapA 和 GapB 均在金黄色葡萄球菌的发病机制中发挥重要作用,这首次表明在任何细菌中,糖酵解和糖异生都在毒力中发挥重要作用。