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Science 325 (5936): 83-87

Copyright © 2009 by the American Association for the Advancement of Science

Meningococcal Type IV Pili Recruit the Polarity Complex to Cross the Brain Endothelium

Mathieu Coureuil,1,* Guillain Mikaty,1 Florence Miller,2,3 Hervé Lécuyer,1,4 Christine Bernard,1 Sandrine Bourdoulous,2,3 Guillaume Duménil,1,{dagger} René-Marc Mège,5 Babette B. Weksler,6 Ignacio A. Romero,7 Pierre-Olivier Couraud,2,3 Xavier Nassif1,4

Abstract: Type IV pili mediate the initial interaction of many bacterial pathogens with their host cells. In Neisseria meningitidis, the causative agent of cerebrospinal meningitis, type IV pili–mediated adhesion to brain endothelial cells is required for bacteria to cross the blood-brain barrier. Here, type IV pili–mediated adhesion of N. meningitidis to human brain endothelial cells was found to recruit the Par3/Par6/PKC{zeta} polarity complex that plays a pivotal role in the establishment of eukaryotic cell polarity and the formation of intercellular junctions. This recruitment leads to the formation of ectopic intercellular junctional domains at the site of bacteria–host cell interaction and a subsequent depletion of junctional proteins at the cell-cell interface with opening of the intercellular junctions of the brain-endothelial interface.

1 Université Paris Descartes, Faculté de Médecine, INSERM (U-570), 75015 Paris, France.
2 Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), 75015 Paris, France.
3 INSERM, U567, 75014 Paris, France.
4 AP-HP, Hôpital Necker-Enfants Malades, Paris F-75015, France.
5 INSERM UMR-S 839, Université Pierre et Marie Curie-Paris6, Institut du Fer à Moulin, 75005 Paris, France.
6 Weill Cornell Medical College, New York, NY 10021, USA.
7 Department of Life Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK.

{dagger} Present address: INSERM U970, Paris Cardiovascular Research Center, Paris F-75015, France.

* To whom correspondence should be addressed. E-mail: mathieu.coureuil{at}inserm.fr


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