S. pneumoniae is a major bacterial pathogen that causes meningitis leading up to 40% mortality. About 50% of survivors present sequelae including learning impairment, deafness, mental retardation and hydrocephalus. We hypothesize that during meningitis caused by S. pneumoniae, bacterial adhesins interaction with their target molecules in the brain contribute to the brain damage: i) directly by altering the brain cells' function and ii) indirectly, by eliciting a strong proinflammatory response, which in turn affect brain cell function. We have previously identified several putative receptors to bacterial adhesin, which are membrane and extracellular matrix proteins known to function in the brain development or affect neural cell function. Currently we demonstrate that a significant inhibition of pneumococcal adhesion to glioblastoma cells (U251) by these recombinant (rNOX, rGtS) adhesins. To study alterations in the functional state of the U251 cells following infection with the pneumococci we tested DNA topoisomerase I activity. The DNA Topoisomerase I is an essential nuclear enzyme that participates in all DNA transaction processes and is important for gene expression. Topoisomerase I activity was found to be significantly reduced in U251 cell upon pneumococcal infection in vitro. In conclusion, the previously identified adhesions and the alteration of topoisomerase I activity in pneumococcal infected cells are suspected to be involved in pneumococcal meningitis development
