Pathogens that are able to cross the blood-brain barrier can cause cerebrospinal meningitis. Pili on the surface of Neisseria meningitidis mediate adhesion to endothelial cells in the brain and are required for crossing the blood-brain barrier, but the mechanism was unclear. A recent report (Science 325, 83–87; 2009) describes how the bacterium breaches the blood-brain barrier.
N. meningitidis hijacks cell-polarity proteins to mislocalize cell-junction components that make up the endothelial cell barrier, allowing bacterial transfer. The authors infected cultured brain endothelial cells with N. meningitides, which adhered to cells, formed microcolonies and recruited actin — events that are known to be triggered by type IV pili. They also found that components of adherens and tight junctions, which are normally located between the cells, appeared underneath bacterial microcolonies. These structures were connected to actin and required the prior recruitment of the polarity proteins Par3 and Par6, as is the case for normal adherens junctions. The adherens junction protein VE-cadherin was shown to relocalize, through endocytosis, from intercellular junctions to the location of the bacteria. Bacterial infection increased cell permeability and resulted in the appearance of gaps between the cells in a manner dependent on the activity of the polarity kinase PKCzeta and bacterial pili. Thus, N. meningitidis subverts a normal polarization pathway to invade the brain. CKR
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