Mechanisms of methicillin-resistant staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis

Erin E. Perrone, Enjae Jung, Elise Breed, Jessica A. Dominguez, Zhe Liang, Andrew T. Clark, W. Michael Dunne, Eileen M. Burd, Craig M. Coopersmith

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced sepsis is a common cause of morbidity in the intensive care unit. Although pneumonia is initiated in the lungs, extrapulmonary manifestations occur commonly. In light of the key role the intestine plays in the pathophysiology of sepsis, we sought to determine whether MRSA pneumonia induces intestinal injury. FVB/N mice were subjected to MRSA or sham pneumonia and killed 24 h later. Septic animals had a marked increase in intestinal epithelial apoptosis by both hematoxylin-eosin and active caspase 3 staining. Methicillin-resistant S. aureus-induced intestinal apoptosis was associated with an increase in the expression of the proapoptotic proteins Bid and Bax and the antiapoptotic protein Bcl-x L in the mitochondrial pathway. In the receptor-mediated pathway, MRSA pneumonia induced an increase in Fas ligand but decreased protein levels of Fas, FADD, pFADD, TNF-R1, and TRADD. To assess the functional significance of these changes, MRSA pneumonia was induced in mice with genetic manipulations in proteins in either the mitochondrial or receptor-mediated pathways. Both Bid -/- mice and animals with intestine-specific overexpression of Bcl-2 had decreased intestinal apoptosis compared with wild-type animals. In contrast, Fas ligand -/- mice had no alterations in apoptosis. To determine if these findings were organism-specific, similar experiments were performed in mice subjected to Pseudomonas aeruginosa pneumonia. Pseudomonas aeruginosa induced gut apoptosis, but unlike MRSA, this was associated with increased Bcl-2 and TNF-R1 and decreased Fas. Methicillin-resistant S. aureus pneumonia thus induces organism-specific changes in intestinal apoptosis via changes in both the mitochondrial and receptor-mediated pathways, although the former may be more functionally significant.

Original languageEnglish (US)
Pages (from-to)68-75
Number of pages8
JournalShock
Volume38
Issue number1
DOIs
StatePublished - Jul 2012
Externally publishedYes

Fingerprint

Staphylococcal Pneumonia
Methicillin-Resistant Staphylococcus aureus
Apoptosis
Pneumonia
Fas Ligand Protein
Pseudomonas aeruginosa
Intestines
Sepsis
BH3 Interacting Domain Death Agonist Protein
bcl-2-Associated X Protein
Wild Animals
Hematoxylin
Eosine Yellowish-(YS)
Caspase 3
Intensive Care Units
Proteins
Staining and Labeling
Morbidity
Lung

Keywords

  • Bax
  • Bcl-2
  • Bid
  • cell death
  • Fas Ligand
  • gut
  • Pseudomonas aeruginosa
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Perrone, E. E., Jung, E., Breed, E., Dominguez, J. A., Liang, Z., Clark, A. T., ... Coopersmith, C. M. (2012). Mechanisms of methicillin-resistant staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis. Shock, 38(1), 68-75. https://doi.org/10.1097/SHK.0b013e318259abdb

Mechanisms of methicillin-resistant staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis. / Perrone, Erin E.; Jung, Enjae; Breed, Elise; Dominguez, Jessica A.; Liang, Zhe; Clark, Andrew T.; Dunne, W. Michael; Burd, Eileen M.; Coopersmith, Craig M.

In: Shock, Vol. 38, No. 1, 07.2012, p. 68-75.

Research output: Contribution to journalArticle

Perrone, EE, Jung, E, Breed, E, Dominguez, JA, Liang, Z, Clark, AT, Dunne, WM, Burd, EM & Coopersmith, CM 2012, 'Mechanisms of methicillin-resistant staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis', Shock, vol. 38, no. 1, pp. 68-75. https://doi.org/10.1097/SHK.0b013e318259abdb
Perrone, Erin E. ; Jung, Enjae ; Breed, Elise ; Dominguez, Jessica A. ; Liang, Zhe ; Clark, Andrew T. ; Dunne, W. Michael ; Burd, Eileen M. ; Coopersmith, Craig M. / Mechanisms of methicillin-resistant staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis. In: Shock. 2012 ; Vol. 38, No. 1. pp. 68-75.
@article{5bfb2f7bfc7442e1a21c7d0e45b16116,
title = "Mechanisms of methicillin-resistant staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis",
abstract = "Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced sepsis is a common cause of morbidity in the intensive care unit. Although pneumonia is initiated in the lungs, extrapulmonary manifestations occur commonly. In light of the key role the intestine plays in the pathophysiology of sepsis, we sought to determine whether MRSA pneumonia induces intestinal injury. FVB/N mice were subjected to MRSA or sham pneumonia and killed 24 h later. Septic animals had a marked increase in intestinal epithelial apoptosis by both hematoxylin-eosin and active caspase 3 staining. Methicillin-resistant S. aureus-induced intestinal apoptosis was associated with an increase in the expression of the proapoptotic proteins Bid and Bax and the antiapoptotic protein Bcl-x L in the mitochondrial pathway. In the receptor-mediated pathway, MRSA pneumonia induced an increase in Fas ligand but decreased protein levels of Fas, FADD, pFADD, TNF-R1, and TRADD. To assess the functional significance of these changes, MRSA pneumonia was induced in mice with genetic manipulations in proteins in either the mitochondrial or receptor-mediated pathways. Both Bid -/- mice and animals with intestine-specific overexpression of Bcl-2 had decreased intestinal apoptosis compared with wild-type animals. In contrast, Fas ligand -/- mice had no alterations in apoptosis. To determine if these findings were organism-specific, similar experiments were performed in mice subjected to Pseudomonas aeruginosa pneumonia. Pseudomonas aeruginosa induced gut apoptosis, but unlike MRSA, this was associated with increased Bcl-2 and TNF-R1 and decreased Fas. Methicillin-resistant S. aureus pneumonia thus induces organism-specific changes in intestinal apoptosis via changes in both the mitochondrial and receptor-mediated pathways, although the former may be more functionally significant.",
keywords = "Bax, Bcl-2, Bid, cell death, Fas Ligand, gut, Pseudomonas aeruginosa, Sepsis",
author = "Perrone, {Erin E.} and Enjae Jung and Elise Breed and Dominguez, {Jessica A.} and Zhe Liang and Clark, {Andrew T.} and Dunne, {W. Michael} and Burd, {Eileen M.} and Coopersmith, {Craig M.}",
year = "2012",
month = "7",
doi = "10.1097/SHK.0b013e318259abdb",
language = "English (US)",
volume = "38",
pages = "68--75",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Mechanisms of methicillin-resistant staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis

AU - Perrone, Erin E.

AU - Jung, Enjae

AU - Breed, Elise

AU - Dominguez, Jessica A.

AU - Liang, Zhe

AU - Clark, Andrew T.

AU - Dunne, W. Michael

AU - Burd, Eileen M.

AU - Coopersmith, Craig M.

PY - 2012/7

Y1 - 2012/7

N2 - Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced sepsis is a common cause of morbidity in the intensive care unit. Although pneumonia is initiated in the lungs, extrapulmonary manifestations occur commonly. In light of the key role the intestine plays in the pathophysiology of sepsis, we sought to determine whether MRSA pneumonia induces intestinal injury. FVB/N mice were subjected to MRSA or sham pneumonia and killed 24 h later. Septic animals had a marked increase in intestinal epithelial apoptosis by both hematoxylin-eosin and active caspase 3 staining. Methicillin-resistant S. aureus-induced intestinal apoptosis was associated with an increase in the expression of the proapoptotic proteins Bid and Bax and the antiapoptotic protein Bcl-x L in the mitochondrial pathway. In the receptor-mediated pathway, MRSA pneumonia induced an increase in Fas ligand but decreased protein levels of Fas, FADD, pFADD, TNF-R1, and TRADD. To assess the functional significance of these changes, MRSA pneumonia was induced in mice with genetic manipulations in proteins in either the mitochondrial or receptor-mediated pathways. Both Bid -/- mice and animals with intestine-specific overexpression of Bcl-2 had decreased intestinal apoptosis compared with wild-type animals. In contrast, Fas ligand -/- mice had no alterations in apoptosis. To determine if these findings were organism-specific, similar experiments were performed in mice subjected to Pseudomonas aeruginosa pneumonia. Pseudomonas aeruginosa induced gut apoptosis, but unlike MRSA, this was associated with increased Bcl-2 and TNF-R1 and decreased Fas. Methicillin-resistant S. aureus pneumonia thus induces organism-specific changes in intestinal apoptosis via changes in both the mitochondrial and receptor-mediated pathways, although the former may be more functionally significant.

AB - Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced sepsis is a common cause of morbidity in the intensive care unit. Although pneumonia is initiated in the lungs, extrapulmonary manifestations occur commonly. In light of the key role the intestine plays in the pathophysiology of sepsis, we sought to determine whether MRSA pneumonia induces intestinal injury. FVB/N mice were subjected to MRSA or sham pneumonia and killed 24 h later. Septic animals had a marked increase in intestinal epithelial apoptosis by both hematoxylin-eosin and active caspase 3 staining. Methicillin-resistant S. aureus-induced intestinal apoptosis was associated with an increase in the expression of the proapoptotic proteins Bid and Bax and the antiapoptotic protein Bcl-x L in the mitochondrial pathway. In the receptor-mediated pathway, MRSA pneumonia induced an increase in Fas ligand but decreased protein levels of Fas, FADD, pFADD, TNF-R1, and TRADD. To assess the functional significance of these changes, MRSA pneumonia was induced in mice with genetic manipulations in proteins in either the mitochondrial or receptor-mediated pathways. Both Bid -/- mice and animals with intestine-specific overexpression of Bcl-2 had decreased intestinal apoptosis compared with wild-type animals. In contrast, Fas ligand -/- mice had no alterations in apoptosis. To determine if these findings were organism-specific, similar experiments were performed in mice subjected to Pseudomonas aeruginosa pneumonia. Pseudomonas aeruginosa induced gut apoptosis, but unlike MRSA, this was associated with increased Bcl-2 and TNF-R1 and decreased Fas. Methicillin-resistant S. aureus pneumonia thus induces organism-specific changes in intestinal apoptosis via changes in both the mitochondrial and receptor-mediated pathways, although the former may be more functionally significant.

KW - Bax

KW - Bcl-2

KW - Bid

KW - cell death

KW - Fas Ligand

KW - gut

KW - Pseudomonas aeruginosa

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=84862753094&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862753094&partnerID=8YFLogxK

U2 - 10.1097/SHK.0b013e318259abdb

DO - 10.1097/SHK.0b013e318259abdb

M3 - Article

VL - 38

SP - 68

EP - 75

JO - Shock

JF - Shock

SN - 1073-2322

IS - 1

ER -