CcpA -Knockout Staphylococcus aureus Induces Abnormal Metabolic Phenotype via the Activation of Hepatic STAT5/PDK4 Signaling in Diabetic Mice.
Yilang LiJiaxuan CaiYinan LiuConglin LiXiaoqing ChenWing-Leung WongWenyue JiangYuan QinGuiping ZhangNing HouWenchang YuanPublished in: Pathogens (Basel, Switzerland) (2023)
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 .
Keyphrases
- high glucose
- endothelial cells
- blood glucose
- wild type
- staphylococcus aureus
- fatty acid
- escherichia coli
- glycemic control
- biofilm formation
- binding protein
- gene expression
- insulin resistance
- cardiovascular disease
- cell proliferation
- poor prognosis
- induced apoptosis
- single cell
- genome wide
- weight loss
- transcription factor
- physical activity
- long non coding rna
- endoplasmic reticulum stress
- cell death
- cell cycle arrest
- weight gain
- small molecule
- machine learning
- high fat diet induced