Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes
ABSTRACT Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks of Staphylococcus aureus colonization and overt infections. S. aureus causes a wide range of severe illnesses in both healthy and immunocompromised indivi...
Guardado en:
Autores principales: | , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
American Society for Microbiology
2015
|
Materias: | |
Acceso en línea: | https://doaj.org/article/a3fe8697edd444cc870955388df674d3 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:a3fe8697edd444cc870955388df674d3 |
---|---|
record_format |
dspace |
spelling |
oai:doaj.org-article:a3fe8697edd444cc870955388df674d32021-11-15T15:41:34ZChronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes10.1128/mBio.02554-142150-7511https://doaj.org/article/a3fe8697edd444cc870955388df674d32015-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02554-14https://doaj.org/toc/2150-7511ABSTRACT Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks of Staphylococcus aureus colonization and overt infections. S. aureus causes a wide range of severe illnesses in both healthy and immunocompromised individuals. Among S. aureus virulence factors, superantigens are essential for pathogenicity. In this study, we show that rabbits that are chronically exposed to S. aureus superantigen toxic shock syndrome toxin-1 (TSST-1) experience impaired glucose tolerance, systemic inflammation, and elevated endotoxin levels in the bloodstream, all of which are common findings in DMII. Additionally, such DMII-associated findings are also seen through effects of TSST-1 on isolated adipocytes. Collectively, our findings suggest that chronic exposure to S. aureus superantigens facilitates the development of DMII, which may lead to therapeutic targeting of S. aureus and its superantigens. IMPORTANCE Obesity has a strong correlation with type 2 diabetes, in which fatty tissue, containing adipocytes, contributes to the development of the illness through altered metabolism and chronic inflammation. The human microbiome changes in persons with obesity and type 2 diabetes, including increases in Staphylococcus aureus colonization and overt infections. While the microbiome is essential for human wellness, there is little understanding of the role of microbes in obesity or the development of diabetes. Here, we demonstrate that the S. aureus superantigen toxic shock syndrome toxin-1 (TSST-1), an essential exotoxin in pathogenesis, induces inflammation, lipolysis, and insulin resistance in adipocytes both in vitro and in vivo. Chronic stimulation of rabbits with TSST-1 results in impaired systemic glucose tolerance, the hallmark finding in type 2 diabetes in humans, suggesting a role of S. aureus and its superantigens in the progression to type 2 diabetes.Bao G. VuChristopher S. StachKatarina KulhankovaWilmara Salgado-PabónAloysius J. KlingelhutzPatrick M. SchlievertAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 2 (2015) |
institution |
DOAJ |
collection |
DOAJ |
language |
EN |
topic |
Microbiology QR1-502 |
spellingShingle |
Microbiology QR1-502 Bao G. Vu Christopher S. Stach Katarina Kulhankova Wilmara Salgado-Pabón Aloysius J. Klingelhutz Patrick M. Schlievert Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes |
description |
ABSTRACT Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks of Staphylococcus aureus colonization and overt infections. S. aureus causes a wide range of severe illnesses in both healthy and immunocompromised individuals. Among S. aureus virulence factors, superantigens are essential for pathogenicity. In this study, we show that rabbits that are chronically exposed to S. aureus superantigen toxic shock syndrome toxin-1 (TSST-1) experience impaired glucose tolerance, systemic inflammation, and elevated endotoxin levels in the bloodstream, all of which are common findings in DMII. Additionally, such DMII-associated findings are also seen through effects of TSST-1 on isolated adipocytes. Collectively, our findings suggest that chronic exposure to S. aureus superantigens facilitates the development of DMII, which may lead to therapeutic targeting of S. aureus and its superantigens. IMPORTANCE Obesity has a strong correlation with type 2 diabetes, in which fatty tissue, containing adipocytes, contributes to the development of the illness through altered metabolism and chronic inflammation. The human microbiome changes in persons with obesity and type 2 diabetes, including increases in Staphylococcus aureus colonization and overt infections. While the microbiome is essential for human wellness, there is little understanding of the role of microbes in obesity or the development of diabetes. Here, we demonstrate that the S. aureus superantigen toxic shock syndrome toxin-1 (TSST-1), an essential exotoxin in pathogenesis, induces inflammation, lipolysis, and insulin resistance in adipocytes both in vitro and in vivo. Chronic stimulation of rabbits with TSST-1 results in impaired systemic glucose tolerance, the hallmark finding in type 2 diabetes in humans, suggesting a role of S. aureus and its superantigens in the progression to type 2 diabetes. |
format |
article |
author |
Bao G. Vu Christopher S. Stach Katarina Kulhankova Wilmara Salgado-Pabón Aloysius J. Klingelhutz Patrick M. Schlievert |
author_facet |
Bao G. Vu Christopher S. Stach Katarina Kulhankova Wilmara Salgado-Pabón Aloysius J. Klingelhutz Patrick M. Schlievert |
author_sort |
Bao G. Vu |
title |
Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes |
title_short |
Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes |
title_full |
Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes |
title_fullStr |
Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes |
title_full_unstemmed |
Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes |
title_sort |
chronic superantigen exposure induces systemic inflammation, elevated bloodstream endotoxin, and abnormal glucose tolerance in rabbits: possible role in diabetes |
publisher |
American Society for Microbiology |
publishDate |
2015 |
url |
https://doaj.org/article/a3fe8697edd444cc870955388df674d3 |
work_keys_str_mv |
AT baogvu chronicsuperantigenexposureinducessystemicinflammationelevatedbloodstreamendotoxinandabnormalglucosetoleranceinrabbitspossibleroleindiabetes AT christophersstach chronicsuperantigenexposureinducessystemicinflammationelevatedbloodstreamendotoxinandabnormalglucosetoleranceinrabbitspossibleroleindiabetes AT katarinakulhankova chronicsuperantigenexposureinducessystemicinflammationelevatedbloodstreamendotoxinandabnormalglucosetoleranceinrabbitspossibleroleindiabetes AT wilmarasalgadopabon chronicsuperantigenexposureinducessystemicinflammationelevatedbloodstreamendotoxinandabnormalglucosetoleranceinrabbitspossibleroleindiabetes AT aloysiusjklingelhutz chronicsuperantigenexposureinducessystemicinflammationelevatedbloodstreamendotoxinandabnormalglucosetoleranceinrabbitspossibleroleindiabetes AT patrickmschlievert chronicsuperantigenexposureinducessystemicinflammationelevatedbloodstreamendotoxinandabnormalglucosetoleranceinrabbitspossibleroleindiabetes |
_version_ |
1718427660663652352 |