Extracellular loops of the Eschericia coli outer membrane protein A contribute to the pathogenesis of meningitis

Ravi Maruvada, Kwang Sik Kim

Research output: Contribution to journalArticle

Abstract

Neonatal meningitis by Eschericia coli RS218 occurs due to bacteremia and its transmigration across the bloodbrain barrier. Although the outermembrane protein A (OmpA), amolecule with extracellular loops has been shown to contribute to the above phenomenon, we do not know the exact the role of these individual loops. Using bacterial strains whose individual loops have been removed, we demonstrated that whereas Loops1 and 2 contribute to 70%-80% bacterial survival in serum, bacterial entry into human brain microvascular endothelial cells (HBMEC) is governed by Loops1, 2, and 3. Cellular invasion was shown to require activation of host cytosolic phospholipase A2 (cPLA2α) by Loops1 and 2 but not 3. This suggests 2 distinct pathways for bacterial entry into host cells. Loop 4 played no role in either serum survival, cellular entry, or cPLA2α signaling. These findings demonstrate for the first time the different contributions of extracellular loops of OmpA to the pathogenesis of E. coli meningitis.

Original languageEnglish (US)
Pages (from-to)131-140
Number of pages10
JournalJournal of Infectious Diseases
Volume203
Issue number1
DOIs
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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