Cytotoxic necrotizing factor-1 contributes to Escherichia coli K1 invasion of the central nervous system

Naveed Ahmed Khan, Ying Wang, Kee Jun Kim, Jin Woong Chung, Carol Ann Wass, Kwang Sik Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Escherichia coli K1 invasion of brain microvascular endothelial cells (BMECs) is a prerequisite for penetration into the central nervous system and requires actin cytoskeletal rearrangements. Here, we demonstrate that E. coli K1 invasion of BMECs requires RhoA activation. In addition, we show that cytotoxic necrotizing factor-1 (CNF1) contributes to E. coli K1 invasion of brain endothelial cells in vitro and traversal of the blood-brain barrier in the experimental hematogenous meningitis animal model. These in vitro and in vivo effects of CNF1 were dependent upon RhoA activation as shown by (a) decreased invasion and RhoA activation with the Δcnf1 mutant of E. coli K1 and (b) restoration of invasion frequency of the Δcnf1 mutant to the level of the parent E. coli K1 strain in BMECs with constitutively active RhoA. In addition, CNF1-enhanced E. coli invasion of brain endothelial cells and stress fiber formation were independent of focal adhesion kinase and phosphatidylinositol 3-kinase activation. This is the first demonstration that CNF1 contributes to E. coli K1 invasion of BMECs.

Original languageEnglish (US)
Pages (from-to)15607-15612
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
StatePublished - May 3 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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