Ca2+/calmodulin-dependent invasion of microvascular endothelial cells of human brain by Escherichia coli K1

Yuri V. Kim, Donna Pearce, Kwang Sik Kim

Research output: Contribution to journalArticle

Abstract

Escherichia coli K1 invasion of microvascular endothelial cells of human brain (HBMEC) is required for E. coli penetration into the central nervous system, but the microbial-host interactions that are involved in this invasion of HBMEC remain incompletely understood. We have previously shown that FimH, one of the E. coli determinants contributing to the binding to and invasion of HBMEC, induces Ca2+ changes in HBMEC. In the present study, we have investigated in detail the role of cellular calcium signaling in the E. coli K1 invasion of HBMEC, the main constituents of the blood-brain barrier. Addition of the meningitis-causing E. coli K1 strain RS218 (O18:K1) to HBMEC results in transient increases of intracellular free Ca2+. Inhibition of phospholipase C with U-73122 and the chelating of intracellular Ca2+ by BAPTA/AM reduces bacterial invasion of HBMEC by approximately 50%. Blocking of transmembrane Ca2+ fluxes by extracellular lanthanum ions also inhibits the E. coli invasion of HBMEC by approximately 50%. In addition, E. coli K1 invasion is significantly inhibited when HBMEC are pretreated by the calmodulin antagonists, trifluoperazine or calmidazolium, or by ML-7, a specific inhibitor of Ca2+/calmodulin-dependent myosin light-chain kinase. These findings indicate that host intracellular Ca2+ signaling contributes in part to E. coli K1 invasion of HBMEC.

Original languageEnglish (US)
Pages (from-to)427-433
Number of pages7
JournalCell and Tissue Research
Volume332
Issue number3
DOIs
StatePublished - Jun 2008

Keywords

  • Brain
  • Calcium signaling
  • Calmodulin
  • Endothelial cells
  • Escherichia coli
  • Human
  • Invasion
  • Myosin light-chain kinase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Fingerprint Dive into the research topics of 'Ca<sup>2+</sup>/calmodulin-dependent invasion of microvascular endothelial cells of human brain by Escherichia coli K1'. Together they form a unique fingerprint.

  • Cite this