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BRAIN DAMAGE IN NEWBORN RAT MODEL OF MENINGITIS BY ENTEROBACTER SAKAZAKII: A ROLE FOR OUTER MEMBRANE PROTEIN A

Enterobacter sakazakii(ES) is an emerging pathogen that causes sepsis, meningitis, and necrotizing enterocolitis in neonates. Very limited information is available regarding the pathogenesis of these diseases and the specific virulence factors of ES. Here, we demonstrate, for the first time using a...

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Autores principales: Mittal, Rahul, Wang, Ying, Hunter, Catherine J., Gonzalez-Gomez, Ignacio, Prasadarao, Nemani V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256236/
https://www.ncbi.nlm.nih.gov/pubmed/19139724
http://dx.doi.org/10.1038/labinvest.2008.164
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author Mittal, Rahul
Wang, Ying
Hunter, Catherine J.
Gonzalez-Gomez, Ignacio
Prasadarao, Nemani V.
author_facet Mittal, Rahul
Wang, Ying
Hunter, Catherine J.
Gonzalez-Gomez, Ignacio
Prasadarao, Nemani V.
author_sort Mittal, Rahul
collection PubMed
description Enterobacter sakazakii(ES) is an emerging pathogen that causes sepsis, meningitis, and necrotizing enterocolitis in neonates. Very limited information is available regarding the pathogenesis of these diseases and the specific virulence factors of ES. Here, we demonstrate, for the first time using a newborn rat model, that outer membrane protein A (OmpA) expression is important for the onset of meningitis by ES. Orally administered OmpA(+) ES traverses the intestinal barrier, multiplies in blood, and subsequently penetrates the blood-brain barrier. OmpA(+) ES were present in high numbers in the brains of infected animals along with associated neutrophil infiltration, hemorrhage, and gliosis. In contrast, OmpA(−) ES could not bind to the intestinal epithelial cells in vitro and in vivo efficiently. The bound OmpA(+) ES also caused apoptosis of enterocytes in the intestinal segments of infected animals; OmpA(−) ES did not. Furthermore, OmpA(−) ES is very susceptible to blood and serum killing whereas OmpA(+) ES is resistant. Of note, 100% mortality rates were observed in OmpA(+) ES infected newborn rats while OmpA(−) ES infected rats survived without any pathological manifestations. The inability of OmpA(−) ES to cause disease was restored by complementation with the ompA gene. These results suggest that OmpA expression in ES is necessary for the colonization of the gastrointestinal tract and for subsequent survival in blood to cause meningitis.
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spelling pubmed-32562362012-01-11 BRAIN DAMAGE IN NEWBORN RAT MODEL OF MENINGITIS BY ENTEROBACTER SAKAZAKII: A ROLE FOR OUTER MEMBRANE PROTEIN A Mittal, Rahul Wang, Ying Hunter, Catherine J. Gonzalez-Gomez, Ignacio Prasadarao, Nemani V. Lab Invest Article Enterobacter sakazakii(ES) is an emerging pathogen that causes sepsis, meningitis, and necrotizing enterocolitis in neonates. Very limited information is available regarding the pathogenesis of these diseases and the specific virulence factors of ES. Here, we demonstrate, for the first time using a newborn rat model, that outer membrane protein A (OmpA) expression is important for the onset of meningitis by ES. Orally administered OmpA(+) ES traverses the intestinal barrier, multiplies in blood, and subsequently penetrates the blood-brain barrier. OmpA(+) ES were present in high numbers in the brains of infected animals along with associated neutrophil infiltration, hemorrhage, and gliosis. In contrast, OmpA(−) ES could not bind to the intestinal epithelial cells in vitro and in vivo efficiently. The bound OmpA(+) ES also caused apoptosis of enterocytes in the intestinal segments of infected animals; OmpA(−) ES did not. Furthermore, OmpA(−) ES is very susceptible to blood and serum killing whereas OmpA(+) ES is resistant. Of note, 100% mortality rates were observed in OmpA(+) ES infected newborn rats while OmpA(−) ES infected rats survived without any pathological manifestations. The inability of OmpA(−) ES to cause disease was restored by complementation with the ompA gene. These results suggest that OmpA expression in ES is necessary for the colonization of the gastrointestinal tract and for subsequent survival in blood to cause meningitis. 2009-01-12 2009-03 /pmc/articles/PMC3256236/ /pubmed/19139724 http://dx.doi.org/10.1038/labinvest.2008.164 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Mittal, Rahul
Wang, Ying
Hunter, Catherine J.
Gonzalez-Gomez, Ignacio
Prasadarao, Nemani V.
BRAIN DAMAGE IN NEWBORN RAT MODEL OF MENINGITIS BY ENTEROBACTER SAKAZAKII: A ROLE FOR OUTER MEMBRANE PROTEIN A
title BRAIN DAMAGE IN NEWBORN RAT MODEL OF MENINGITIS BY ENTEROBACTER SAKAZAKII: A ROLE FOR OUTER MEMBRANE PROTEIN A
title_full BRAIN DAMAGE IN NEWBORN RAT MODEL OF MENINGITIS BY ENTEROBACTER SAKAZAKII: A ROLE FOR OUTER MEMBRANE PROTEIN A
title_fullStr BRAIN DAMAGE IN NEWBORN RAT MODEL OF MENINGITIS BY ENTEROBACTER SAKAZAKII: A ROLE FOR OUTER MEMBRANE PROTEIN A
title_full_unstemmed BRAIN DAMAGE IN NEWBORN RAT MODEL OF MENINGITIS BY ENTEROBACTER SAKAZAKII: A ROLE FOR OUTER MEMBRANE PROTEIN A
title_short BRAIN DAMAGE IN NEWBORN RAT MODEL OF MENINGITIS BY ENTEROBACTER SAKAZAKII: A ROLE FOR OUTER MEMBRANE PROTEIN A
title_sort brain damage in newborn rat model of meningitis by enterobacter sakazakii: a role for outer membrane protein a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256236/
https://www.ncbi.nlm.nih.gov/pubmed/19139724
http://dx.doi.org/10.1038/labinvest.2008.164
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