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CcpA-Knockout Staphylococcus aureus Induces Abnormal Metabolic Phenotype via the Activation of Hepatic STAT5/PDK4 Signaling in Diabetic Mice

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 dia...

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Autores principales: Li, Yilang, Cai, Jiaxuan, Liu, Yinan, Li, Conglin, Chen, Xiaoqing, Wong, Wing-Leung, Jiang, Wenyue, Qin, Yuan, Zhang, Guiping, Hou, Ning, Yuan, Wenchang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674825/
https://www.ncbi.nlm.nih.gov/pubmed/38003764
http://dx.doi.org/10.3390/pathogens12111300
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author Li, Yilang
Cai, Jiaxuan
Liu, Yinan
Li, Conglin
Chen, Xiaoqing
Wong, Wing-Leung
Jiang, Wenyue
Qin, Yuan
Zhang, Guiping
Hou, Ning
Yuan, Wenchang
author_facet Li, Yilang
Cai, Jiaxuan
Liu, Yinan
Li, Conglin
Chen, Xiaoqing
Wong, Wing-Leung
Jiang, Wenyue
Qin, Yuan
Zhang, Guiping
Hou, Ning
Yuan, Wenchang
author_sort Li, Yilang
collection PubMed
description 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.
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spelling pubmed-106748252023-10-30 CcpA-Knockout Staphylococcus aureus Induces Abnormal Metabolic Phenotype via the Activation of Hepatic STAT5/PDK4 Signaling in Diabetic Mice Li, Yilang Cai, Jiaxuan Liu, Yinan Li, Conglin Chen, Xiaoqing Wong, Wing-Leung Jiang, Wenyue Qin, Yuan Zhang, Guiping Hou, Ning Yuan, Wenchang Pathogens Article 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. MDPI 2023-10-30 /pmc/articles/PMC10674825/ /pubmed/38003764 http://dx.doi.org/10.3390/pathogens12111300 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Yilang
Cai, Jiaxuan
Liu, Yinan
Li, Conglin
Chen, Xiaoqing
Wong, Wing-Leung
Jiang, Wenyue
Qin, Yuan
Zhang, Guiping
Hou, Ning
Yuan, Wenchang
CcpA-Knockout Staphylococcus aureus Induces Abnormal Metabolic Phenotype via the Activation of Hepatic STAT5/PDK4 Signaling in Diabetic Mice
title CcpA-Knockout Staphylococcus aureus Induces Abnormal Metabolic Phenotype via the Activation of Hepatic STAT5/PDK4 Signaling in Diabetic Mice
title_full CcpA-Knockout Staphylococcus aureus Induces Abnormal Metabolic Phenotype via the Activation of Hepatic STAT5/PDK4 Signaling in Diabetic Mice
title_fullStr CcpA-Knockout Staphylococcus aureus Induces Abnormal Metabolic Phenotype via the Activation of Hepatic STAT5/PDK4 Signaling in Diabetic Mice
title_full_unstemmed CcpA-Knockout Staphylococcus aureus Induces Abnormal Metabolic Phenotype via the Activation of Hepatic STAT5/PDK4 Signaling in Diabetic Mice
title_short CcpA-Knockout Staphylococcus aureus Induces Abnormal Metabolic Phenotype via the Activation of Hepatic STAT5/PDK4 Signaling in Diabetic Mice
title_sort ccpa-knockout staphylococcus aureus induces abnormal metabolic phenotype via the activation of hepatic stat5/pdk4 signaling in diabetic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674825/
https://www.ncbi.nlm.nih.gov/pubmed/38003764
http://dx.doi.org/10.3390/pathogens12111300
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