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.

The Journal of Biological Chemistry
Sascha KarassekM Alexander Schmidt

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 messeng...Continue Reading

References

Sep 17, 1992·The New England Journal of Medicine·V Quagliarello, W M Scheld
May 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·T Katada, M Ui
Jul 1, 1980·The Histochemical Journal·K T Tokuyasu
Jun 1, 1994·Infection and Immunity·G D ArmstrongL D Heerze
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·S W Jeong, S R Ikeda
Aug 14, 2001·Infection and Immunity·K S Kim
Mar 6, 2002·The Journal of Biological Chemistry·Naveed Ahmed KhanKwang Sik Kim
Nov 9, 2002·The Journal of Infectious Diseases·Kwang Sik Kim
May 3, 2003·Nature Reviews. Neuroscience·Kwang Sik Kim
Jul 3, 2004·Pediatrics·Ulrich HeiningerUNKNOWN Sudden Infant Death Syndrome Study Group
Oct 13, 2004·FEMS Immunology and Medical Microbiology·Yi XieKwang Sik Kim
Apr 13, 2005·Biochemical and Biophysical Research Communications·Sooan ShinKwang-Sik Kim
Jun 1, 2005·Trends in Immunology·Michael K RackeAmy E Lovett-Racke
Nov 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Henrik Toft-HansenTrevor Owens
Jan 16, 2007·Cellular Microbiology·Naveed Ahmed KhanKwang Sik Kim
Jun 19, 2008·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·V HoudouinE Bingen
Jul 8, 2008·Nature Reviews. Microbiology·Kwang Sik Kim
Feb 24, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Anita K M ZaidiUNKNOWN Sindh Meningitis Group
Mar 14, 2009·Archives de pédiatrie : organe officiel de la Sociéte française de pédiatrie·V HoudouinE Bingen
Dec 8, 2009·Nature Reviews. Microbiology·Matthew A Croxen, B Brett Finlay
Feb 23, 2010·Kansenshōgaku zasshi. The Journal of the Japanese Association for Infectious Diseases·Keisuke SunakawaYoshitake Sato
Mar 17, 2010·The Journal of Biological Chemistry·Motohiro NishidaHitoshi Kurose
May 2, 2012·Fluids and Barriers of the CNS·Angela E SchellenbergJames Peeling
Sep 18, 2013·The Journal of Infectious Diseases·Subramanian KrishnanNemani V Prasadarao

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