Brain damage in newborn rat model of meningitis by Enterobacter sakazakii: A role for outer membrane protein A

Rahul Mittal, Ying Wang, Catherine J. Hunter, Ignacio Gonzalez-Gomez, Nemani V. Prasadarao

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

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 are very susceptible to blood and serum killing, whereas OmpA+ ES are resistant. Of note, 100% mortality rates were observed in OmpA+ ES-infected newborn rats, whereas 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.

Original languageEnglish (US)
Pages (from-to)263-277
Number of pages15
JournalLaboratory Investigation
Volume89
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • Enterobacter sakazakii
  • Meningitis
  • Outer membrane protein A
  • Rat brain
  • Survival

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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