PDF(Pubmed)
Abstract：
Catabolite control protein A (CcpA), an important global regulatory protein, is extensively found in S. aureus. Many studies have reported that CcpA plays a pivotal role in regulating the tricarboxylic acid cycle and pathogenicity. Moreover, the CcpA-knockout Staphylococcus aureus (S. aureus) in diabetic mice, compared with the wild-type, showed a reduced colonization rate in the tissues and organs and decreased inflammatory factor expression. However, the effect of CcpA-knockout S. aureus on the host\'s energy metabolism in a high-glucose environment and its mechanism of action remain unclear. S. aureus, a common and major human pathogen, is increasingly found in patients with obesity and diabetes, as recent clinical data reveal. To address this issue, we generated CcpA-knockout S. aureus strains with different genetic backgrounds to conduct in-depth investigations. In vitro experiments with high-glucose-treated cells and an in vivo model study with type 1 diabetic mice were used to evaluate the unknown effect of CcpA-knockout strains on both the glucose and lipid metabolism phenotypes of the host. We found that the strains caused an abnormal metabolic phenotype in type 1 diabetic mice, particularly in reducing random and fasting blood glucose and increasing triglyceride and fatty acid contents in the serum. In a high-glucose environment, CcpA-knockout S. aureus may activate the hepatic STAT5/PDK4 pathway and affect pyruvate utilization. An abnormal metabolic phenotype was thus observed in diabetic mice. Our findings provide a better understanding of the molecular mechanism of glucose and lipid metabolism disorders in diabetic patients infected with S. aureus.
摘要：
代谢产物控制蛋白A(CcpA),一种重要的全球调节蛋白，广泛存在于金黄色葡萄球菌中。许多研究报道，CpA在调节三羧酸循环和致病性中起关键作用。此外，CpA敲除的金黄色葡萄球菌(S.金黄色葡萄球菌)在糖尿病小鼠中，与野生型相比，组织器官定殖率降低,炎症因子表达降低。然而,CpA基因敲除的金黄色葡萄球菌在高糖环境中对宿主能量代谢的影响及其作用机制尚不清楚。金黄色葡萄球菌，一种常见和主要的人类病原体，越来越多地出现在肥胖和糖尿病患者中，正如最近的临床数据显示。为了解决这个问题，我们产生了具有不同遗传背景的CpA基因敲除金黄色葡萄球菌菌株,以进行深入研究.使用高葡萄糖处理的细胞的体外实验和1型糖尿病小鼠的体内模型研究来评估CpA敲除菌株对宿主的葡萄糖和脂质代谢表型的未知影响。我们发现这些菌株在1型糖尿病小鼠中引起了异常的代谢表型，特别是降低随机和空腹血糖，增加血清中甘油三酯和脂肪酸含量。在高葡萄糖环境中,CpA敲除金黄色葡萄球菌可激活肝STAT5/PDK4途径并影响丙酮酸利用。因此在糖尿病小鼠中观察到异常代谢表型。我们的发现为金黄色葡萄球菌感染的糖尿病患者糖脂代谢紊乱的分子机制提供了更好的理解。
