THE INVOLVEMENT OF S. PNEUMONIAE CELL-WALL ADHESINS IN INHIBITION OF TOPOISOMERASE I ENZYME AND INTERACTION WITH THE HOST CELLS

S. pneumoniae is a commensal pathogen that colonizes the nasopharynx asymptomatically. However, it may cause otitis media, pneumonia, and bacteremia and is currently the leading cause of meningitis in infants.

Pneumococcal adhesion is a prerequisite for disease development. Several cell-wall proteins of S. pneumoniae (FlaR, NOX, PTS^man, ABC transporter, TF and PepV), were found by us to mediate interaction with lung derived epithelial (A549), neuronal (NSC34) and glial (U251) cells in vitro and in vivo via specific host target receptors.

Currently, we examine the effect of the adhesion on topoisomerase I (Topo I) activity, an essential enzyme for all the DNA transaction processes and the target of anti-cancer drugs. Adhesion of the pathogen to the above target cells resulted in inhibition of Topo I enzyme (Topo I) activity.

However, null mutant strains, lacking one of the adhesins, demonstrated reduced adhesion to all the cell lines tested, compared to the wild type WU2 strain. Consistently, Topo I activity was significantly restored following the infection with the null mutants.

Complementation of the null mutant bacteria with the respective gene reestablished ability to adhere to the host cells was accompanied by restored inhibition of Topo I activity in all of the tested cell lines, similarly to the effects exerted by the wild type strain.

Combined, these results imply that interaction of these adhesins with their correspondent receptors on the host cells triggers specific intracellular pathways that exert their inhibitory effect on Topo I.