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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2009
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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. |
format | Online Article Text |
id | pubmed-3256236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
record_format | MEDLINE/PubMed |
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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