Pertussis toxin exploits specific host cell signaling pathways for promoting invasion and translocation of Escherichia coli K1 RS218 in human brain-derived microvascular endothelial cells

Sascha Karassek, Laura Starost, Johanna Solbach, Lilo Greune, Yasuteru Sano, Takashi Kanda, Kwangsik Kim, M. Alexander Schmidt

Research output: Contribution to journalArticlepeer-review

Abstract

Pertussis toxin (PTx), an AB5 toxin and major virulence factor of the whooping cough-causing pathogen Bordetella pertussis, has been shown to affect the blood-brain barrier. Dysfunction of the blood-brain barrier may facilitate penetration of bacterial pathogens into the brain, such as Escherichia coli K1 (RS218). In this study, we investigated the influence of PTx on blood-brain barrier permissiveness to E. coli infection using human brain-derived endothelial HBMEC and TY10 cells as in vitro models. Our results indicate that PTx acts at several key points of host cell intracellular signaling pathways, which are also affected by E. coli K1 RS218 infection. Application of PTx increased the expression of the pathogen binding receptor gp96. Further, we found an activation of STAT3 and of the small GTPase Rac1, which have been described as being essential for bacterial invasion involving host cell actin cytoskeleton rearrangements at the bacterial entry site. In addition, we showed that PTx induces a remarkable relocation of VE-cadherin and β-catenin from intercellular junctions. The observed changes in host cell signaling molecules were accompanied by differences in intracellular calcium levels, which might act as a second messenger system for PTx. In summary, PTx not only facilitates invasion of E. coli K1 RS218 by activating essential signaling cascades; it also affects intercellular barriers to increase paracellular translocation.

Original languageEnglish (US)
Pages (from-to)24835-24843
Number of pages9
JournalJournal of Biological Chemistry
Volume290
Issue number41
DOIs
StatePublished - Oct 9 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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