Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.

Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the...

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Main Authors: Yiorgos Apidianakis, Michael N Mindrinos, Wenzhong Xiao, George P Tegos, Michail I Papisov, Michael R Hamblin, Ronald W Davis, Ronald G Tompkins, Laurence G Rahme
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-12-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001356&type=printable
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author Yiorgos Apidianakis
Michael N Mindrinos
Wenzhong Xiao
George P Tegos
Michail I Papisov
Michael R Hamblin
Ronald W Davis
Ronald G Tompkins
Laurence G Rahme
author_facet Yiorgos Apidianakis
Michael N Mindrinos
Wenzhong Xiao
George P Tegos
Michail I Papisov
Michael R Hamblin
Ronald W Davis
Ronald G Tompkins
Laurence G Rahme
author_sort Yiorgos Apidianakis
collection DOAJ
description Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals.
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publisher Public Library of Science (PLoS)
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spelling doaj-art-5410d6b7992c484083fdc4b07a1bb33f2025-08-20T02:38:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-12-01212e135610.1371/journal.pone.0001356Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.Yiorgos ApidianakisMichael N MindrinosWenzhong XiaoGeorge P TegosMichail I PapisovMichael R HamblinRonald W DavisRonald G TompkinsLaurence G RahmeDespite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001356&type=printable
spellingShingle Yiorgos Apidianakis
Michael N Mindrinos
Wenzhong Xiao
George P Tegos
Michail I Papisov
Michael R Hamblin
Ronald W Davis
Ronald G Tompkins
Laurence G Rahme
Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.
PLoS ONE
title Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.
title_full Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.
title_fullStr Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.
title_full_unstemmed Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.
title_short Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.
title_sort involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001356&type=printable
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